Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Pathogenic
- Review status:
- reviewed by expert panel
- Submissions:
- 67
- First in ClinVar:
- Apr 12, 2013
- Most recent Submission:
- Mar 11, 2023
- Last evaluated:
- Apr 22, 2016
- Accession:
- VCV000009325.95
- Variation ID:
- 9325
- Description:
- 1bp deletion
Help
NM_000059.4(BRCA2):c.5946del (p.Ser1982fs)
- Allele ID
- 24364
- Variant type
- Deletion
- Variant length
- 1 bp
- Cytogenetic location
- 13q13.1
- Genomic location
- 13: 32340301 (GRCh38) GRCh38 UCSC
- 13: 32914438 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000059.4:c.5946del MANE Select NP_000050.3:p.Ser1982fs frameshift NM_000059.3:c.5946delT NC_000013.11:g.32340301del NC_000013.10:g.32914438del NG_012772.3:g.29822del LRG_293:g.29822del U43746.1:n.6174delT - Protein change
- S1982fs
- Other names
- NP_000050.3:p.Ser1982ArgfsTer22
- 6174delT
- Canonical SPDI
- NC_000013.11:32340300:T:
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- Trans-Omics for Precision Medicine (TOPMed) 0.00011
- NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00016
- The Genome Aggregation Database (gnomAD) 0.00019
- Trans-Omics for Precision Medicine (TOPMed) 0.00010
- The Genome Aggregation Database (gnomAD) 0.00016
- Exome Aggregation Consortium (ExAC) 0.00027
- The Genome Aggregation Database (gnomAD), exomes 0.00029
- Links
- Breast Cancer Information Core (BIC) (BRCA2): 6174&base_change=del T
- ClinGen: CA023403
- Genetic Testing Registry (GTR): GTR000520122
- Genetic Testing Registry (GTR): GTR000558872
- Genetic Testing Registry (GTR): GTR000560788
- Genetic Testing Registry (GTR): GTR000566692
- OMIM: 600185.0005
- OMIM: 600185.0009
- dbSNP: rs80359550
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 23 | reviewed by expert panel | Apr 22, 2016 | RCV000009910.31 | |
| Pathogenic | 10 | criteria provided, multiple submitters, no conflicts | Nov 2, 2022 | RCV000034451.34 | |
| Pathogenic | 3 | criteria provided, multiple submitters, no conflicts | Nov 3, 2021 | RCV000044800.13 | |
| Pathogenic | 6 | criteria provided, multiple submitters, no conflicts | Oct 23, 2021 | RCV000129627.13 | |
| Pathogenic | 17 | criteria provided, multiple submitters, no conflicts | Oct 28, 2022 | RCV000212245.36 | |
| Pathogenic | 1 | criteria provided, single submitter | Apr 28, 2017 | RCV000367838.5 | |
| Pathogenic | 1 | criteria provided, single submitter | - | RCV000414179.2 | |
| Pathogenic | 1 | criteria provided, single submitter | Mar 6, 2022 | RCV000768632.3 | |
| risk factor | 1 | no assertion criteria provided | Sep 12, 2016 | RCV000009911.6 | |
| Pathogenic | 1 | no assertion criteria provided | Sep 12, 2016 | RCV000009912.6 | |
| Pathogenic | 1 | no assertion criteria provided | Dec 1, 2018 | RCV000785226.3 | |
| Pathogenic | 1 | no assertion criteria provided | Feb 21, 2023 | RCV003128125.1 | |
| not provided | 1 | no assertion provided | - | RCV001535431.2 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
17000 | 17140 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Apr 22, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282418.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Nov 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories,University of Michigan
Accession: SCV000195993.1
First in ClinVar: Feb 26, 2016 Last updated: Feb 26, 2016 |
Tissue: Blood
|
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Pathogenic
(-)
|
criteria provided, single submitter
Method: research
|
Breast Cancer
Affected status: yes
Allele origin:
germline
|
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center
Accession: SCV000492446.1
First in ClinVar: Jan 09, 2017 Last updated: Jan 09, 2017 |
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Pathogenic
(Feb 23, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Baylor Genetics
Accession: SCV000540997.1
First in ClinVar: Dec 17, 2016 Last updated: Dec 17, 2016 |
Number of individuals with the variant: 1
|
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Pathogenic
(Feb 12, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000575747.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
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Pathogenic
(Jul 12, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000679720.1
First in ClinVar: Oct 21, 2017 Last updated: Oct 21, 2017 |
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Pathogenic
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
|
BRCA2-Related Disorders
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000383728.3
First in ClinVar: Dec 06, 2016 Last updated: May 27, 2019 |
Comment:
The BRCA2 c.5946delT (p.Ser1982ArgfsTer22) variant, more commonly known as c.6174delT, results in a frameshift and premature termination of the protein. The p.Ser1982ArgfsTer22 variant is a … (more)
The BRCA2 c.5946delT (p.Ser1982ArgfsTer22) variant, more commonly known as c.6174delT, results in a frameshift and premature termination of the protein. The p.Ser1982ArgfsTer22 variant is a well-described founder variant in the BRCA2 gene that is prevalent in the Ashkenazi Jewish and Icelandic populations, with a carrier frequency of ~1.5% (Roa et al. 1996; Neuhausen et al. 1996). The variant has been shown to occur in approximately eight percent of women diagnosed with breast cancer before the age of 42 years (Neuhausen et al. 1996; Oddoux et al. 1996; Petrucelli et al. 2010; Finkelman et al. 2012). By the age of 70, 43% of individuals who carry this variant are predicted to develop breast cancer and 20% are predicted to develop ovarian cancer (Struewing et al. 1997; King et al. 2003). Across a selection of the literature, the p.Ser1982ArgfsTer22 variant has been identified in 55 of 1,272 (4%) individuals with breast cancer, 44 of 382 (11.5%) individuals with ovarian cancer, and at least 118 of 9,658 (1.2%) Ashkenazi Jewish individuals from the general population (Couch et al. 1996; Roa et al. 1996; Neuhausen et al. 1996; Oddoux et al. 1996; Struewing et al. 1997; Satagopan et al. 2002; King et al. 2003). Additionally, the p.Ser1982ArgfsTer22 variant has been identified in a compound heterozygous state in four individuals, including two cousins, with Fanconi anemia and brain tumors from three different Ashkenazi Jewish families (Offit et al. 2003; Alter et al. 2007). The p.Ser1982ArgfsTer22 variant was absent from at least 1,726 non-Ashkenazi Jewish controls and is reported at a frequency of 0.00048 in the European (non-Finnish) population of the Exome Aggregation Consortium. Functional studies demonstrated decreased cell viability and survival in carriers of the p.Ser1982ArgfsTer22 variant (Wu et al. 2005). The variant protein was shown to be localized in the cytoplasm and not in the nucleus. The p.Ser1982ArgfsTer22 variant is predicted to result in truncation of approximately 41% of the BRCA2 protein, which would remove two signals required for nuclear localization and represents a likely mode of pathogenicity for the variant (Spain et al. 1999). In a study in mouse embryonic stem cells, the p.Ser1982ArgfsTer22 variant failed to rescue the loss of endogenous BRCA2 (Kuznetsov et al. 2008). Based on the collective evidence, the p.Ser1982ArgfsTer22 variant is classified as pathogenic for BRCA2-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Aug 14, 2018)
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criteria provided, single submitter
Method: clinical testing
|
Cancer Syndrome, Hereditary
Affected status: yes
Allele origin:
germline
|
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV000996186.1
First in ClinVar: Oct 20, 2019 Last updated: Oct 20, 2019 |
Comment:
This variant is also known as c.6174delT using alternate nomenclature. This variant is known as a founder mutation in the Ashkenazi Jewish population (PMID: 20301425) … (more)
This variant is also known as c.6174delT using alternate nomenclature. This variant is known as a founder mutation in the Ashkenazi Jewish population (PMID: 20301425) and has been previously reported as a heterozygous change in multiple individuals with a personal or family history of breast and/or ovarian cancer, among other types of cancer (PMID: 20301425, 29084914, 29433453, 2644092, 29321669, 28767289). Based on the available evidence, the c.5946delT (p.Ser1982ArgfsTer22) variant is classified as pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(May 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918979.2
First in ClinVar: Jun 03, 2019 Last updated: Nov 10, 2019 |
Comment:
Variant summary: BRCA2 c.5946delT (p.Ser1982ArgfsX22) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA2 c.5946delT (p.Ser1982ArgfsX22) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.0002765 in 282088 control chromosomes (gnomAD), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503) and was predominantly observed in the Ashkenazi Jewish subpopulation. This variant is a well-established Ashkenazi Jewish founder mutation. The variant, c.5946delT, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Abeliovich_1997, Friedman_1998). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Wu_2005). Multiple ClinVar submissions after 2014 cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Apr 24, 2019)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000605785.3
First in ClinVar: Aug 27, 2017 Last updated: Jul 06, 2020 |
Comment:
The p.Ser1982ArgfsX22 variant in BRCA2 is a founder mutation in the Ashkenazi Jewish population (Finkelman 2012) and has been identified in >500 individuals of various … (more)
The p.Ser1982ArgfsX22 variant in BRCA2 is a founder mutation in the Ashkenazi Jewish population (Finkelman 2012) and has been identified in >500 individuals of various ethnicities with BRCA2-associated cancers (Breast Cancer Information Core (BIC) database: https://research.nhgri.nih.gov/projects/bic/). It has also been identified in 0.6% (61/10364) of Ashkenazi Jewish and 0.01% (14/128890) of European chromosomes by gnomAD, http://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1982 and leads to a premature termination codon 22 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function BRCA2 is an established disease mechanism for hereditary breast and ovarian cancer (HBOC) syndrome. Additionally, this variant was classified as pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000282418.1). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC based upon the predicted impact to the protein and presence in multiple affected individuals. ACMG/AMP Criteria applied: PVS1, PS4_Strong. (less)
Number of individuals with the variant: 19
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Pathogenic
(Aug 07, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital
Accession: SCV001450241.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 17
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Pathogenic
(Oct 19, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000778694.2
First in ClinVar: Sep 28, 2017 Last updated: Jun 08, 2021 |
Number of individuals with the variant: 3
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Pathogenic
(Jan 04, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001934380.1
First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
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Pathogenic
(Oct 23, 2021)
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criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4,Sema4
Accession: SCV002536189.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA2 c.5946delT (p.S1982RfsX22) variant is a well characterized pathogenic variant that has been associated with autosomal dominant hereditary breast and ovarian cancer syndrome (PMID: … (more)
The BRCA2 c.5946delT (p.S1982RfsX22) variant is a well characterized pathogenic variant that has been associated with autosomal dominant hereditary breast and ovarian cancer syndrome (PMID: 9042909). This variant is also known as 6174delT in the literature. This variant is a founder pathogenic variant in the Ashkenazi Jewish population (PMID: 9042909, 9150153) and it has been reported in individuals of other ethnicities as well (PMID: 8758903, 10417300). This variant causes a frameshift at amino acid 1982 that results in premature termination 22 amino acids downstream. This variant is expected to result in an absent or non-functional protein product (loss of function). Loss of function variants in BRCA2 are known to be pathogenic (PMID: 29446198). This variant was observed in 61/10364 chromosomes in the Ashkenazi Jewish subpopulation, with no homozygotes, according to the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654) and has been reported in ClinVar (Variation ID: 9325). Based on the current evidence available, this variant was interpreted as pathogenic. (less)
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Pathogenic
(May 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV002570374.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
This variant (rs28897738) has been reported in the literature in association with a variety of BRCA2-related cancer conditions that are inherited in a dominant or … (more)
This variant (rs28897738) has been reported in the literature in association with a variety of BRCA2-related cancer conditions that are inherited in a dominant or recessive manner. It is known as a founder mutation in the Ashkenazi Jewish population and has also been observed in individuals of non-Ashkenazi Jewish descent. It is rare (<0.1%) in a large population dataset (gnomAD: 78/282088 total alleles; 0.0277%; no homozygotes) and has been reported in ClinVar(Variation ID 9325). This frameshift variant results in a premature stop codon in exon 11, likely leading to nonsense-mediated decay and lack of protein production and has supporting functional evidence. We consider this variant to be pathogenic. (less)
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Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000327312.4
First in ClinVar: Jun 24, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Jul 01, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Department of Medical Genetics, Oslo University Hospital
Accession: SCV000605651.3
First in ClinVar: Jul 27, 2017 Last updated: Dec 11, 2022 |
Number of individuals with the variant: 11
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Pathogenic
(Apr 17, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia,Australian Genomics
Accession: SCV002761748.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
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Pathogenic
(Mar 31, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
New York Genome Center
Accession: SCV002764549.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Comment:
The c.5946del, p.Ser1982ArgfsTer22 missense variant identified in BRCA2, also known as c.6174delT, results in a frameshift and premature termination of the protein. The p.Ser1982ArgfsTer22 variant … (more)
The c.5946del, p.Ser1982ArgfsTer22 missense variant identified in BRCA2, also known as c.6174delT, results in a frameshift and premature termination of the protein. The p.Ser1982ArgfsTer22 variant is a founder variant in the BRCA2 gene that is prevalent in the Ashkenazi Jewish and Icelandic populations, and has been previously reported as a heterozygous change in multiple individuals with a personal or family history of breast and/or ovarian cancer, among other types of cancer (PMID: 20301425, 29084914, 29433453, 29321669, 28767289). Based on the available evidence, the c.5946delT, p.Ser1982ArgfsTer22 variant is classified as pathogenic. (less)
Observation 1:
Clinical Features:
Hyperlipidemia (present) , Diabetes mellitus (present)
Zygosity: 1 Single Heterozygote
Secondary finding: yes
Observation 2:
Clinical Features:
Hyperlipidemia (present) , Hepatic steatosis (present)
Zygosity: 1 Single Heterozygote
Secondary finding: yes
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Pathogenic
(Apr 07, 2014)
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criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000154098.2
First in ClinVar: Jun 09, 2014 Last updated: Dec 24, 2022 |
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Pathogenic
(Aug 19, 2021)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296747.6
First in ClinVar: Jun 24, 2016 Last updated: Dec 31, 2022 |
Comment:
This frameshift variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. The frequency of this … (more)
This frameshift variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. The frequency of this variant in the general population, 0.00011 (14/128890 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported as a BRCA2 founder variant in the Ashkenazi Jewish population with a carrier frequency of approximately 1.52% (PMID: 17591843 (2007) and 8841191 (1996)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jun 11, 2020)
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criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000108631.16
First in ClinVar: Dec 10, 2013 Last updated: Mar 04, 2023 |
Comment:
Common founder variant in the Ashkenazi Jewish population (Oddoux 1996); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene … (more)
Common founder variant in the Ashkenazi Jewish population (Oddoux 1996); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect: increased sensitivity to MMC, decreased HDR, and increased centrosome amplification compared to wild-type (Wu 2005); Observed in approximately 1% of the Ashkenazi Jewish population (Oddoux 1996); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 6174delT; This variant is associated with the following publications: (PMID: 20736950, 20887823, 28049106, 28291774, 30620386, 27836010, 23633455, 15695382, 19188187, 22703879, 22009639, 22430266, 23658460, 23341105, 22006311, 21324516, 8673091, 25980754, 26440929, 27425403, 14559878, 26681312, 29321669, 29339979, 29433453, 29368341, 29084914, 27989354, 29907814, 26556299, 10464624, 28767289, 8841192, 29161300, 29439820, 30274973, 30152102, 29506128, 30122538, 30716324, 30186769, 30720243, 29961768, 30702160, 29978187, 30322717, 29937315, 30113427, 30489631, 31263054, 31444830, 32438681, 31512090, 29625052, 26689913, 31447099, 31948886, 34308366, 10739756, 10733239, 34399810, 33077847, 31589614, 32853339, 32341426, 32719484, 32885271, 32338768, 30787465, 30613976, 33087929) (less)
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Pathogenic
(Mar 06, 2022)
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criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000219371.5 First in ClinVar: Mar 29, 2015 Last updated: Mar 11, 2023 |
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Pathogenic
(May 16, 2016)
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criteria provided, single submitter
Method: clinical testing
|
{Breast-ovarian cancer, familial, 2}
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory,University of Chicago
Accession: SCV000593749.1
First in ClinVar: Jul 27, 2017 Last updated: Jul 27, 2017 |
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Pathogenic
(Sep 21, 2015)
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criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744479.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Nov 07, 2017)
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criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: no
Allele origin:
unknown
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Study: Clinvar_gadteam_Clinical_exome_analysis_3
Accession: SCV000803796.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Mar 03, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics,PreventionGenetics
Accession: SCV000805732.1
First in ClinVar: Sep 28, 2017 Last updated: Sep 28, 2017 |
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Pathogenic
(Sep 16, 2018)
|
criteria provided, single submitter
Method: research
|
not provided
Affected status: yes
Allele origin:
germline
|
Gharavi Laboratory,Columbia University
Accession: SCV000809465.1
First in ClinVar: Sep 28, 2017 Last updated: Sep 28, 2017 |
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Pathogenic
(May 24, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000839905.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
The c.5946del (p.Ser1982Argfs*22) variant has been detected in a multiple patients with breast and ovarian cancer [reported as c.6174del in PMID 8673091, 23633455, 22006311, 21324516, … (more)
The c.5946del (p.Ser1982Argfs*22) variant has been detected in a multiple patients with breast and ovarian cancer [reported as c.6174del in PMID 8673091, 23633455, 22006311, 21324516, 22430266]. The variant was also detected in patients with prostate cancer [PMID 19188187, 20736950] and pancreatic ductal adenocarcinoma [PMID 23658460]. This variant is associated with a cancer risk of 50-43% and 18-20% risk for breast and ovarian cancer respectively by age 70 [PMID 9145676,15994883]. In vitro assays showed that this variant leads to a loss of function of the protein [PMID 15695382]. This variant has been reported in 32 non-Finnish Europeans from the ExAC database (http://exac.broadinstitute.org/variant/13-32914437-GT-G). This c.5946del (p.Ser1982Argfs*22) variant occurs at high frequency in the Ashkenazi Jewish population and is considered a founder mutation in this population. This variant is thus classified as pathogenic.[leduc, 2017-03-07] (less)
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|
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Pathogenic
(Feb 03, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins NTD LLC (GA)
Accession: SCV000225181.5
First in ClinVar: Jun 28, 2015 Last updated: Sep 28, 2017 |
Number of individuals with the variant: 5
Zygosity: 5 Single Heterozygote
Sex: mixed
|
|
|
Pathogenic
(Jan 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000693574.2
First in ClinVar: Sep 28, 2017 Last updated: May 04, 2020 |
Comment:
This variant is a deletion of one nucleotide, resulting in a frameshift and the creation of a novel translational stop codon after 22 amino acid … (more)
This variant is a deletion of one nucleotide, resulting in a frameshift and the creation of a novel translational stop codon after 22 amino acid residues. The protein product thus produced is truncated and non-functional. Truncating variants in BRCA2 are known to be pathogenic. In the literature, this variant is also known as 6174delT and is a common cause of breast and ovarian cancer in the Ashkenazi Jewish population (PMID: 9042909, 22430266). Moreover, it has been reported in individuals of other ethnicities (PMID: 8758903, 10417300). This variant has been associated with a 43% to 55% risk of breast cancer by age 70, and a 20% to 37% risk of ovarian cancer by age 70 (PMID: 15994883). The mutation database ClinVar contains entries for this variant (Variation ID: 9325). (less)
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|
|
Pathogenic
(Dec 15, 2020)
|
criteria provided, single submitter
Method: research
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: no
Allele origin:
germline
|
Department of Pediatrics,Memorial Sloan Kettering Cancer Center
Accession: SCV001478111.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
|
|
|
Pathogenic
(Jun 17, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762173.1
First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021 |
Clinical Features:
Neoplasm of the pancreas (present)
Sex: male
|
|
|
Pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010347.1
First in ClinVar: Nov 06, 2021 Last updated: Nov 06, 2021 |
|
|
|
Pathogenic
(Nov 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002025788.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Geographic origin: South Africa
Testing laboratory: National Health Laboratory Service (NHLS)
|
|
|
Pathogenic
(Feb 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000292121.4
First in ClinVar: Jul 08, 2016 Last updated: Jan 08, 2022 |
Comment:
This variant (also known as 6174delT) deletes 1 nucleotide in exon 11 of the BRCA2 gene, causing a frameshift and a premature translational stop signal. … (more)
This variant (also known as 6174delT) deletes 1 nucleotide in exon 11 of the BRCA2 gene, causing a frameshift and a premature translational stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is a well-known founder mutation in the Ashkenazi Jewish population and occurs at 0.6-1.52% minor allele frequency (PMID: 30152102). This variant has been reported in numerous individuals affected with breast and ovarian cancer in Ashkenazi Jewish population (PMID: 8673092, 9042909, 9150153, 15994883, 22430266, 30152102), as well as in non-Ashkenazi Jewish population. The risk of female breast cancer among carriers of this mutation is 43-55% by age 70, and the risk of ovarian cancer is 18-37% by age 70 (PMID: 9145676, 15994883, 22430266). This variant has been identified in 78/282088 chromosomes in the general population (61/10364 Ashkenazi Jewish chromosomes) by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic. (less)
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|
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Pathogenic
(Aug 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002581177.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PS4
|
Number of individuals with the variant: 2
Sex: female
|
|
|
Pathogenic
(Sep 24, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000184420.7
First in ClinVar: Aug 06, 2014 Last updated: Nov 29, 2022 |
Comment:
The c.5946delT pathogenic mutation is located in coding exon 10 of the BRCA2 gene and is one of the well-described Ashkenazi Jewish founder mutations. This … (more)
The c.5946delT pathogenic mutation is located in coding exon 10 of the BRCA2 gene and is one of the well-described Ashkenazi Jewish founder mutations. This mutation results from a deletion of one nucleotide at position 5946, causing a translational frameshift with a predicted alternate stop codon (p.S1982Rfs*22). This mutation has been reported in numerous families affected with breast, ovarian, prostate, pancreatic, and other HBOC-related cancers (Agalliu I et al. Clin. Cancer Res. 2009 Feb;15:1112-20; Walsh T et al. Proc. Natl. Acad. Sci. USA. 2011 Nov;108:18032-7; Johnston JJ et al. Am. J. Hum. Genet. 2012 Jul;91:97-108; Bayraktar S et al. Cancer. 2012 Mar;118:1515-22; George J et al. Clin. Cancer Res. 2013 Jul;19:3474-84; Lucas AL et al. Clin. Cancer Res. 2013 Jul;19:3396-403; Salo-Mullen EE et al. Cancer. 2015 Dec;121:4382-8; Susswein LR et al. Genet. Med. 2016 Aug;18:823-32). Another study indicated that carriers of the c.5946delT mutation may have a lower relative risk for breast cancer when compared to carriers of other non-Ashkenazi Jewish BRCA2 mutations (Finkelman BS et al. J. Clin. Oncol. 2012 Apr;30:1321-8). This mutation is also designated as 6174delT in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Jul 02, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV000838826.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Mar 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV002526014.2
First in ClinVar: Jun 18, 2022 Last updated: Dec 24, 2022 |
Comment:
The BRCA2 c.5946del (p.Ser1982ArgfsTer22) change causes a frameshift and the creation of a premature stop codon. This change is predicted to cause protein truncation or … (more)
The BRCA2 c.5946del (p.Ser1982ArgfsTer22) change causes a frameshift and the creation of a premature stop codon. This change is predicted to cause protein truncation or absence of the protein due to nonsense mediated decay (PVS1). This variant has a maximum subpopulation frequency of 0.59% in gnomAD v2.1.1, where it is primarily found in the Ashkenazi Jewish population (https://gnomad.broadinstitute.org/variant/13-32914437-GT-G?dataset=gnomad_r2_1). This variant has been reported in multiple individuals with breast cancer and/or ovarian cancer (PMID: 8673092, 9042909, 9150153, 15994883, 22430266, 30152102). It is a well-established pathogenic founder variant in the Ashkenazi Jewish population (PMID: 9042909, 22430266). This alteration is also known as 6174delT in the literature. In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria: PVS1, PS4. (less)
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|
|
Pathogenic
(Feb 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001501475.8
First in ClinVar: Mar 14, 2021 Last updated: Jan 21, 2023 |
Number of individuals with the variant: 4
|
|
|
Pathogenic
(Nov 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000072813.16
First in ClinVar: Jul 03, 2013 Last updated: Feb 07, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser1982Argfs*22) in the BRCA2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ser1982Argfs*22) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80359550, gnomAD 0.6%). This premature translational stop signal has been observed in individual(s) with breast (43% to 55% lifetime risk) and/or ovarian cancer (20% to 37% lifetime risk) (PMID: 8758903, 9042909, 10417300, 15994883, 22430266). It is commonly reported in individuals of Ashkenazi Jewish ancestry (PMID: 8758903, 9042909, 10417300, 22430266). This premature translational stop signal has been observed to co-occur in individuals with a different variant in BRCA2 that has been determined to be pathogenic (Invitae), but the significance of this finding is unclear. This variant is also known as 6174delT. ClinVar contains an entry for this variant (Variation ID: 9325). For these reasons, this variant has been classified as Pathogenic. (less)
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|
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Pathogenic
(Apr 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602754.7
First in ClinVar: Sep 28, 2017 Last updated: Mar 04, 2023 |
Comment:
The BRCA2 c.5946delT; p.Ser1982ArgfsTer22 variant (rs80359550), also published as 6174delT, is reported as a pathogenic founder variant in the Ashkenazi Jewish population (Abeliovich 1997, Couch … (more)
The BRCA2 c.5946delT; p.Ser1982ArgfsTer22 variant (rs80359550), also published as 6174delT, is reported as a pathogenic founder variant in the Ashkenazi Jewish population (Abeliovich 1997, Couch 1996, Finkelman 2012), and has been associated with hereditary breast and ovarian cancer syndrome. The variant is reported as pathogenic by several sources in the ClinVar database (Variation ID: 9325) and is found in the Ashkenazi Jewish population with an allele frequency of 0.6% (61/10,364 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Abeliovich D et al. The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet. 1997 Mar;60(3):505-14. Couch FJ et al. BRCA2 germline mutations in male breast cancer cases and breast cancer families. Nat Genet. 1996 May;13(1):123-5. Finkelman BS et al. Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers. J Clin Oncol. 2012 Apr 20;30(12):1321-8. (less)
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|
|
Pathogenic
(Oct 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PerkinElmer Genomics
Accession: SCV002019064.2
First in ClinVar: Nov 29, 2021 Last updated: Mar 11, 2023 |
|
|
|
pathogenic
(Jul 13, 2012)
|
no assertion criteria provided
Method: research
|
Breast-ovarian cancer, familial
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section,National Institutes of Health
Study: ClinSeq
Accession: SCV000043218.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Pathogenic.
Observation 1:
Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
Age: 50-59 years
Sex: male
Ethnicity/Population group: Ashkenazi Jewish
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
Observation 2:
Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
Age: 60-69 years
Sex: male
Ethnicity/Population group: Ashkenazi Jewish
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
Observation 3:
Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
Age: 50-59 years
Sex: male
Ethnicity/Population group: Ashkenazi Jewish
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
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|
|
Pathogenic
(Jul 24, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: unknown
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000189906.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
|
|
|
Pathogenic
(Aug 01, 2015)
|
no assertion criteria provided
Method: research
|
BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer
Affected status: no
Allele origin:
germline
|
Curoverse
Accession: SCV000245334.1
First in ClinVar: Aug 31, 2015 Last updated: Aug 31, 2015 |
Comment:
Frameshifts in BRCA2 are considered pathogenic, and this is a BRCA2 Ser1982Arg frameshift variant in exon 11
Number of individuals with the variant: 1
Age: 40-49 years
Sex: male
|
|
|
Pathogenic
(Jan 15, 2013)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000054198.6
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2016 |
|
|
|
Pathogenic
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587812.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
|
|
|
Pathogenic
(Sep 27, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
True Health Diagnostics
Accession: SCV000787938.1
First in ClinVar: Oct 21, 2017 Last updated: Oct 21, 2017 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000592016.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The BRCA2 p.Ser1982Argfs*22 variant was identified in 33 of 11966 proband chromosomes (frequency: 0.003) from individuals or families with breast, ovarian and pancreatic cancer (Agalliu … (more)
The BRCA2 p.Ser1982Argfs*22 variant was identified in 33 of 11966 proband chromosomes (frequency: 0.003) from individuals or families with breast, ovarian and pancreatic cancer (Agalliu 2009, Borg 2010, Couch 2014, Edwards 2010, Zhang 2011). The variant was also identified in dbSNP (ID: rs80359550) as “With Pathogenic allele”, ClinVar (classified as pathogenic by 34 submitters including Invitae, GeneDx, Counsyl, ARUP and Ambry Genetics), COGR (3 entries classified as pathogenic), COSMIC (1x confirmed somatic in adenocarcinoma of the pancreas), LOVD 3.0 (110 entries classified as affects function), UMD-LSDB (75 entries classified as causal), BIC Database (1090 entries classified as pathogenic), ARUP Laboratories (classified as definitely pathogenic), and the Zhejiang Colon Cancer Database (classified as pathogenic). The variant was not identified in the MutDB database. The variant was also identified by our laboratory in multiple individuals with breast, ovarian or pancreatic cancer. The variant was identified in control databases in 72 of 276978 chromosomes at a frequency of 0.0003 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: Ashkenazi Jewish in 59 of 10150 chromosomes (freq: 0.006), Other in 3 of 6460 chromosomes (freq: 0.0005), European (Non-Finnish) in 10 of 126512 chromosomes (freq: 0.00008); it was not observed in the African, East Asian, European (Finnish), Latino, or South Asian populations. The c.5946delT variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1982 and leads to a premature stop codon 22 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. The truncating BRCA2 6174delT Ashkenazi Jewish founder mutation is associated with a breast cancer risk of 70% by age 70 and identified in the vast majority of Ashkenazi Jewish families with a history of breast and ovarian cancer (Pohlreich 2005, Wu 2005). In addition, a functional study using bacterial artificial chromosomes concluded that this mutation could not rescue lethality in BRCA2-deficient mouse embryonic stem cells, supporting its classification as deleterious (Kuznetsov 2008). In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. Assessment Date: 2018/03/07. (less)
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|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906091.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002037347.1 First in ClinVar: Dec 25, 2021 Last updated: Dec 25, 2021 |
|
|
|
Pathogenic
(Nov 03, 2022)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550357.2
First in ClinVar: Jul 23, 2022 Last updated: Dec 17, 2022 |
|
|
|
Pathogenic
(Feb 21, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Endometrial carcinoma
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV003804351.1
First in ClinVar: Feb 25, 2023 Last updated: Feb 25, 2023 |
Number of individuals with the variant: 1
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
|
|
|
Pathogenic
(Dec 21, 1995)
|
no assertion criteria provided
Method: literature only
|
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000030127.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 26, 2015 |
Comment on evidence:
In 2 families from Montreal with breast-ovarian cancer (BROVCA2; 612555), Wooster et al. (1995) found a T deletion and an AAAC deletion (600185.0006), respectively, in … (more)
In 2 families from Montreal with breast-ovarian cancer (BROVCA2; 612555), Wooster et al. (1995) found a T deletion and an AAAC deletion (600185.0006), respectively, in the BRCA2 gene. Both of these families included a male breast cancer case; previous analyses had indicated that the large majority of such families have BRCA2 mutations (Stratton et al., 1994). (less)
|
|
|
Pathogenic
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline,
unknown
|
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000146737.2
First in ClinVar: Apr 01, 2014 Last updated: Oct 11, 2015 |
Observation 1:
Number of individuals with the variant: 185
Observation 2:
Number of individuals with the variant: 69
Geographic origin: Ashkenazi
Observation 3:
Number of individuals with the variant: 1
Geographic origin: Ashkenazi, Western European
Observation 4:
Number of individuals with the variant: 1
Geographic origin: Ashkenazi, Western, Central/Eastern European
Observation 5:
Number of individuals with the variant: 2
Geographic origin: Austria
Observation 6:
Number of individuals with the variant: 1
Geographic origin: Canada
Observation 7:
Number of individuals with the variant: 2
Geographic origin: Central/Eastern European
Observation 8:
Number of individuals with the variant: 2
Geographic origin: Netherlands
Observation 9:
Number of individuals with the variant: 1
Geographic origin: German French
Observation 10:
Number of individuals with the variant: 1
Geographic origin: Russia
Observation 11:
Number of individuals with the variant: 4
Geographic origin: Western European
Observation 12:
Number of individuals with the variant: 694
Ethnicity/Population group: Ashkenazi
Observation 13:
Number of individuals with the variant: 6
Ethnicity/Population group: Ashkenazi
Geographic origin: American
Observation 14:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi Jewish
Geographic origin: Canada
Observation 15:
Number of individuals with the variant: 19
Ethnicity/Population group: Ashkenazi, Central/Eastern European
Observation 16:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Central/Eastern European, Italian
Observation 17:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Central/Eastern European, Russian
Observation 18:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Latin American, Caribbean
Observation 19:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Latin American, Caribbean, Mex
Observation 20:
Number of individuals with the variant: 2
Ethnicity/Population group: Ashkenazi, Western European
Observation 21:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Western, Eastern, Central European
Observation 22:
Number of individuals with the variant: 1
Ethnicity/Population group: Asian
Observation 23:
Number of individuals with the variant: 1
Ethnicity/Population group: Cacasian
Observation 24:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Observation 25:
Number of individuals with the variant: 2
Ethnicity/Population group: Caucasian
Geographic origin: Netherlands
Observation 26:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Italy
Observation 27:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian Non Hispanic
Observation 28:
Number of individuals with the variant: 12
Ethnicity/Population group: Central/Eastern European
Observation 29:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European, Jewish
Observation 30:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European, Russian Polish
Observation 31:
Number of individuals with the variant: 1
Ethnicity/Population group: Czech, Hungarian, Russian, Jewish
Observation 32:
Number of individuals with the variant: 1
Ethnicity/Population group: Dutch
Observation 33:
Number of individuals with the variant: 11
Ethnicity/Population group: Jewish
Observation 34:
Number of individuals with the variant: 1
Ethnicity/Population group: Jewish
Geographic origin: Chile
Observation 35:
Number of individuals with the variant: 1
Ethnicity/Population group: Jewish
Geographic origin: Sweden
Observation 36:
Number of individuals with the variant: 1
Ethnicity/Population group: Jewish, Polish
Observation 37:
Number of individuals with the variant: 1
Ethnicity/Population group: Latin American, Caribbean, Western European
Observation 38:
Number of individuals with the variant: 1
Ethnicity/Population group: Near Eastern Mid East
Observation 39:
Number of individuals with the variant: 25
Ethnicity/Population group: Western European
Observation 40:
Number of individuals with the variant: 18
Ethnicity/Population group: Western European, Ashkenazi
Observation 41:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ashkenazi, Central, Eas
Observation 42:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ashkenazi, English
Observation 43:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ashkenazi, French Ca
Observation 44:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ashkenazi, French, Jewish
Observation 45:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ashkenazi, Irish, Italian
Observation 46:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Central/Eastern European
Observation 47:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, German, Jewish
Observation 48:
Number of individuals with the variant: 1
Ethnicity/Population group: Western Europeanan, Central/Eastern European
Observation 49:
Number of individuals with the variant: 6
|
|
|
Pathogenic
(Jun 10, 2015)
|
no assertion criteria provided
Method: research
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: not applicable
Allele origin:
not applicable
|
Centro de Genética y Biología Molecular, Universidad de San Martín de Porres
Study: Mutational analysis of BRCA1 and BRCA2 genes in peruvian families with hereditary breast and ovarian cancer
Accession: SCV000263344.1 First in ClinVar: Feb 26, 2016 Last updated: Feb 26, 2016 |
Sex: female
Tissue: Blood
Comment on evidence:
Phatogenic mutation
|
|
|
risk factor
(Sep 12, 2016)
|
no assertion criteria provided
Method: literature only
|
PANCREATIC CANCER, SUSCEPTIBILITY TO, 2
Affected status: not provided
Allele origin:
not provided
|
OMIM
Accession: SCV000030132.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 16, 2016 |
|
|
|
Pathogenic
(Sep 12, 2016)
|
no assertion criteria provided
Method: literature only
|
FANCONI ANEMIA, COMPLEMENTATION GROUP D1
Affected status: not provided
Allele origin:
not provided
|
OMIM
Accession: SCV000030133.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 16, 2016 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare
Accession: SCV000484936.1
First in ClinVar: Dec 17, 2016 Last updated: Dec 17, 2016 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733276.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(Dec 01, 2018)
|
no assertion criteria provided
Method: research
|
Neoplasm of ovary
Affected status: yes
Allele origin:
germline
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923794.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798609.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001926441.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
|
|
|
not provided
(-)
|
no assertion provided
Method: literature only
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV000086654.3
First in ClinVar: Oct 01, 2013 Last updated: Oct 01, 2022 |
Comment:
Founder variant in Ashkenazi Jews; accounts for 95% of pathogenic variants in this population
|
|
|
not provided
(-)
|
no assertion provided
Method: phenotyping only
|
Hereditary breast ovarian cancer syndrome
Fanconi anemia complementation group D1
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749320.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
Variant reported in multiple Invitae PIN participants. Variant interpreted as Pathogenic and reported most recently on 7/5/2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are … (more)
Variant reported in multiple Invitae PIN participants. Variant interpreted as Pathogenic and reported most recently on 7/5/2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Non-Hodgkin lymphoma (present) , Family history of cancer (present)
Indication for testing: Diagnostic
Age: 50-59 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2017-11-22
Testing laboratory interpretation: Pathogenic
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Family history (present) , Family history of cancer (present)
Indication for testing: Presymptomatic|Family Testing
Age: 70-79 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2018-07-05
Testing laboratory interpretation: Pathogenic
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Prevalence of Clinically Relevant Germline BRCA Variants in a Large Unselected South African Breast and Ovarian Cancer Cohort: A Public Sector Experience. | Van der Merwe NC | Frontiers in genetics | 2022 | DOI: 10.3389/fgene.2022.834265 |
| BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. | Adam MP | - | 2022 | PMID: 20301425 |
| BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. | Adam MP | - | 2022 | BookShelf: NBK1247 |
| Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program participants. | Murali K | Hereditary cancer in clinical practice | 2021 | PMID: 34399810 |
| Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric solid tumors. | Fiala EM | Nature cancer | 2021 | PMID: 34308366 |
| Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario. | Lerner-Ellis J | Journal of cancer research and clinical oncology | 2021 | PMID: 32885271 |
| Germline Sequencing DNA Repair Genes in 5545 Men With Aggressive and Nonaggressive Prostate Cancer. | Darst BF | Journal of the National Cancer Institute | 2021 | PMID: 32853339 |
| Exome sequencing and characterization of 49,960 individuals in the UK Biobank. | Van Hout CV | Nature | 2020 | PMID: 33087929 |
| Pathogenic germline variants are associated with poor survival in stage III/IV melanoma patients. | Aoude LG | Scientific reports | 2020 | PMID: 33077847 |
| Population genetic screening efficiently identifies carriers of autosomal dominant diseases. | Grzymski JJ | Nature medicine | 2020 | PMID: 32719484 |
| Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. | De Talhouet S | Scientific reports | 2020 | PMID: 32341426 |
| Rare germline genetic variants and risk of aggressive prostate cancer. | Nguyen-Dumont T | International journal of cancer | 2020 | PMID: 32338768 |
| Rare Germline Pathogenic Mutations of DNA Repair Genes Are Most Strongly Associated with Grade Group 5 Prostate Cancer. | Wu Y | European urology oncology | 2020 | PMID: 31948886 |
| Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma. | Zhang L | Human mutation | 2020 | PMID: 31444830 |
| Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. | Capalbo A | PLoS genetics | 2019 | PMID: 31589614 |
| Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. | eMERGE Consortium. Electronic address: agibbs@bcm.edu | American journal of human genetics | 2019 | PMID: 31447099 |
| Frequency of Pathogenic Germline Variants in CDH1, BRCA2, CHEK2, PALB2, BRCA1, and TP53 in Sporadic Lobular Breast Cancer. | Petridis C | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2019 | PMID: 31263054 |
| Deleterious Germline Mutations Are a Risk Factor for Neoplastic Progression Among High-Risk Individuals Undergoing Pancreatic Surveillance. | Abe T | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2019 | PMID: 30883245 |
| Toward automation of germline variant curation in clinical cancer genetics. | Ravichandran V | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 30787465 |
| High prevalence of cancer-associated TP53 variants in the gnomAD database: A word of caution concerning the use of variant filtering. | Soussi T | Human mutation | 2019 | PMID: 30720243 |
| Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms. | Skaro M | Gastroenterology | 2019 | PMID: 30716324 |
| Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. | Bhaskaran SP | International journal of cancer | 2019 | PMID: 30702160 |
| Ampullary cancer: Evaluation of somatic and germline genetic alterations and association with clinical outcomes. | Wong W | Cancer | 2019 | PMID: 30620386 |
| Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy. | Rizzolo P | International journal of cancer | 2019 | PMID: 30613976 |
| Uterine cancer in Jewish Israeli BRCA1/2 mutation carriers. | Laitman Y | Cancer | 2019 | PMID: 30489631 |
| Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. | Yurgelun MB | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 29961768 |
| Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
| High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer. | Bannon SA | Cancer prevention research (Philadelphia, Pa.) | 2018 | PMID: 30274973 |
| BRCA1 and BRCA2 Mutations Other Than the Founder Alleles Among Ashkenazi Jewish in the Population of Argentina. | Solano AR | Frontiers in oncology | 2018 | PMID: 30186769 |
| Hereditary cancer screening: Case reports and review of literature on ten Ashkenazi Jewish founder mutations. | Cox DM | Molecular genetics & genomic medicine | 2018 | PMID: 30152102 |
| Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot. | Sapp JC | American journal of human genetics | 2018 | PMID: 30122538 |
| Germline Variants and Risk for Pancreatic Cancer: A Systematic Review and Emerging Concepts. | Zhan W | Pancreas | 2018 | PMID: 30113427 |
| Prevalence of Germline Mutations in Cancer Susceptibility Genes in Patients With Advanced Renal Cell Carcinoma. | Carlo MI | JAMA oncology | 2018 | PMID: 29978187 |
| Durable response in a woman with recurrent low-grade endometrioid endometrial cancer and a germline BRCA2 mutation treated with a PARP inhibitor. | Gockley AA | Gynecologic oncology | 2018 | PMID: 29937315 |
| The germline mutational landscape of BRCA1 and BRCA2 in Brazil. | Palmero EI | Scientific reports | 2018 | PMID: 29907814 |
| Pathogenic Germline Variants in 10,389 Adult Cancers. | Huang KL | Cell | 2018 | PMID: 29625052 |
| Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms. | Lowery MA | Journal of the National Cancer Institute | 2018 | PMID: 29506128 |
| Frequency of BRCA1 and BRCA2 causative founder variants in ovarian cancer patients in South-East Poland. | Kluz T | Hereditary cancer in clinical practice | 2018 | PMID: 29492181 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| Germline DNA-repair Gene Mutations and Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Receiving First-line Abiraterone and Enzalutamide. | Antonarakis ES | European urology | 2018 | PMID: 29439820 |
| Male BRCA mutation carriers: clinical characteristics and cancer spectrum. | Ibrahim M | BMC cancer | 2018 | PMID: 29433453 |
| Intraductal/ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer. | Isaacsson Velho P | The Prostate | 2018 | PMID: 29368341 |
| BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. | Heramb C | Hereditary cancer in clinical practice | 2018 | PMID: 29339979 |
| Phenotypic characteristics of colorectal cancer in BRCA1/2 mutation carriers. | Grinshpun A | European journal of human genetics : EJHG | 2018 | PMID: 29321669 |
| Cost effectiveness of population based BRCA1 founder mutation testing in Sephardi Jewish women. | Patel S | American journal of obstetrics and gynecology | 2018 | PMID: 29288066 |
| Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer. | Labidi-Galy SI | Clinical cancer research : an official journal of the American Association for Cancer Research | 2018 | PMID: 29084914 |
| BRCA1 and BRCA2 mutational profile and prevalence in hereditary breast and ovarian cancer (HBOC) probands from Southern Brazil: Are international testing criteria appropriate for this specific population? | Alemar B | PloS one | 2017 | PMID: 29161300 |
| Mutational analysis of BRCA1 and BRCA2 genes in Peruvian families with hereditary breast and ovarian cancer. | Buleje J | Molecular genetics & genomic medicine | 2017 | PMID: 28944232 |
| Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing. | Mandelker D | JAMA | 2017 | PMID: 28873162 |
| Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma. | Shindo K | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2017 | PMID: 28767289 |
| Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. | Nykamp K | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28492532 |
| Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death. | Na R | European urology | 2017 | PMID: 27989354 |
| Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women. | Rebbeck TR | Breast cancer research : BCR | 2016 | PMID: 27836010 |
| Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations. | Alemar B | Cancer genetics | 2016 | PMID: 27425403 |
| Sanger Sequencing for BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del Mutation Screen on Pap Smear Cytology Samples. | Lee SH | International journal of molecular sciences | 2016 | PMID: 26867194 |
| Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
| Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. | Schrader KA | JAMA oncology | 2016 | PMID: 26556299 |
| Patterns and functional implications of rare germline variants across 12 cancer types. | Lu C | Nature communications | 2015 | PMID: 26689913 |
| Identification of germline genetic mutations in patients with pancreatic cancer. | Salo-Mullen EE | Cancer | 2015 | PMID: 26440929 |
| Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory. | Strom CM | PloS one | 2015 | PMID: 26295337 |
| Characterization of medulloblastoma in Fanconi Anemia: a novel mutation in the BRCA2 gene and SHH molecular subgroup. | Miele E | Biomarker research | 2015 | PMID: 26064523 |
| Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome. | Yurgelun MB | Gastroenterology | 2015 | PMID: 25980754 |
| Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
| Hereditary breast and ovarian cancer: assessment of point mutations and copy number variations in Brazilian patients. | Silva FC | BMC medical genetics | 2014 | PMID: 24884479 |
| High prevalence of BRCA1 and BRCA2 germline mutations with loss of heterozygosity in a series of resected pancreatic adenocarcinoma and other neoplastic lesions. | Lucas AL | Clinical cancer research : an official journal of the American Association for Cancer Research | 2013 | PMID: 23658460 |
| Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations. | George J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2013 | PMID: 23633455 |
| Comprehensive analysis of BRCA1, BRCA2 and TP53 germline mutation and tumor characterization: a portrait of early-onset breast cancer in Brazil. | Carraro DM | PloS one | 2013 | PMID: 23469205 |
| Heterozygous mutations in the PALB2 hereditary breast cancer predisposition gene impact on the three-dimensional nuclear organization of patient-derived cell lines. | Wark L | Genes, chromosomes & cancer | 2013 | PMID: 23341105 |
| Novel BRCA1 and BRCA2 pathogenic mutations in Slovene hereditary breast and ovarian cancer families. | Novaković S | International journal of oncology | 2012 | PMC3583621 |
| Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. | Johnston JJ | American journal of human genetics | 2012 | PMID: 22703879 |
| Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers. | Finkelman BS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2012 | PMID: 22430266 |
| Predictive factors for BRCA1/BRCA2 mutations in women with ductal carcinoma in situ. | Bayraktar S | Cancer | 2012 | PMID: 22009639 |
| Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. | Walsh T | Proceedings of the National Academy of Sciences of the United States of America | 2011 | PMID: 22006311 |
| Management of women with BRCA mutations: a 41-year-old woman with a BRCA mutation and a recent history of breast cancer. | Tung N | JAMA | 2011 | PMID: 21558506 |
| Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. | Zhang S | Gynecologic oncology | 2011 | PMID: 21324516 |
| Reactive lymphoid hyperplasia in association with 22q11.2 deletion syndrome and a BRCA2 mutation. | Veerapandiyan A | European journal of medical genetics | 2011 | PMID: 20887823 |
| Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. | Janavičius R | The EPMA journal | 2010 | PMID: 23199084 |
| Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis. | Edwards SM | British journal of cancer | 2010 | PMID: 20736950 |
| Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2. | Petrucelli N | Genetics in medicine : official journal of the American College of Medical Genetics | 2010 | PMID: 20216074 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| Fanconi anemia and biallelic BRCA2 mutation diagnosed in a young child with an embryonal CNS tumor. | Dewire MD | Pediatric blood & cancer | 2009 | PMID: 19530235 |
| Associations of high-grade prostate cancer with BRCA1 and BRCA2 founder mutations. | Agalliu I | Clinical cancer research : an official journal of the American Association for Cancer Research | 2009 | PMID: 19188187 |
| Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2. | Kuznetsov SG | Nature medicine | 2008 | PMID: 18607349 |
| Founder mutations in BRCA1 and BRCA2 genes. | Ferla R | Annals of oncology : official journal of the European Society for Medical Oncology | 2007 | PMID: 17591843 |
| Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. | Alter BP | Journal of medical genetics | 2007 | PMID: 16825431 |
| Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies. | Antoniou AC | Journal of medical genetics | 2005 | PMID: 15994883 |
| Functional evaluation and cancer risk assessment of BRCA2 unclassified variants. | Wu K | Cancer research | 2005 | PMID: 15695382 |
| Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. | King MC | Science (New York, N.Y.) | 2003 | PMID: 14576434 |
| Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia. | Offit K | Journal of the National Cancer Institute | 2003 | PMID: 14559878 |
| Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. | Satagopan JM | Clinical cancer research : an official journal of the American Association for Cancer Research | 2002 | PMID: 12473589 |
| A low frequency of non-founder BRCA1 mutations in Ashkenazi Jewish breast-ovarian cancer families. | Phelan CM | Human mutation | 2002 | PMID: 12402332 |
| Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. | Frank TS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2002 | PMID: 11896095 |
| The frequency of founder mutations in the BRCA1, BRCA2, and APC genes in Australian Ashkenazi Jews: implications for the generality of U.S. population data. | Bahar AY | Cancer | 2001 | PMID: 11466700 |
| BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. | Moslehi R | American journal of human genetics | 2000 | PMID: 10739756 |
| An unaffected individual from a breast/ovarian cancer family with germline mutations in both BRCA1 and BRCA2. | Moslehi R | Clinical genetics | 2000 | PMID: 10733239 |
| Truncated BRCA2 is cytoplasmic: implications for cancer-linked mutations. | Spain BH | Proceedings of the National Academy of Sciences of the United States of America | 1999 | PMID: 10570174 |
| De novo BRCA1 mutation in a patient with breast cancer and an inherited BRCA2 mutation. | Tesoriero A | American journal of human genetics | 1999 | PMID: 10417300 |
| Double heterozygotes for the Ashkenazi founder mutations in BRCA1 and BRCA2 genes. | Friedman E | American journal of human genetics | 1998 | PMID: 9758598 |
| BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and ovarian cancer. | Schubert EL | Genetic testing | 1997 | PMID: 10464624 |
| Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. | Levy-Lahad E | American journal of human genetics | 1997 | PMID: 9150153 |
| The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. | Struewing JP | The New England journal of medicine | 1997 | PMID: 9145676 |
| The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. | Abeliovich D | American journal of human genetics | 1997 | PMID: 9042909 |
| The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%. | Oddoux C | Nature genetics | 1996 | PMID: 8841192 |
| Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. | Roa BB | Nature genetics | 1996 | PMID: 8841191 |
| A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish Ashkenazi and non-Jewish individuals. | Berman DB | Cancer research | 1996 | PMID: 8758903 |
| Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. | Neuhausen S | Nature genetics | 1996 | PMID: 8673092 |
| BRCA2 germline mutations in male breast cancer cases and breast cancer families. | Couch FJ | Nature genetics | 1996 | PMID: 8673091 |
| Identification of the breast cancer susceptibility gene BRCA2. | Wooster R | Nature | 1995 | PMID: 8524414 |
| Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q. | Stratton MR | Nature genetics | 1994 | PMID: 8075631 |
| http://jama.jamanetwork.com/article.aspx?articleid=2214084 | - | - | - | - |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2 | - | - | - | - |
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583621/ | - | - | - | - |
| - | - | - | - | DOI: 10.1001/jama.2011.678 |
Text-mined citations for rs80359550...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
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Record last updated Mar 26, 2023