ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.5722_5723del (p.Leu1908fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.5722_5723del (p.Leu1908fs)
Variation ID: 9320 Accession: VCV000009320.87
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 13q13.1 13: 32340073-32340074 (GRCh38) [ NCBI UCSC ] 13: 32914210-32914211 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 26, 2015 Aug 25, 2024 Apr 22, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.5722_5723del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Leu1908fs frameshift NM_000059.3:c.5718_5719del NM_000059.3:c.5722_5723delCT NC_000013.11:g.32340073CT[2] NC_000013.10:g.32914210CT[2] NG_012772.3:g.29594CT[2] NG_012772.3:g.29598_29599del LRG_293:g.29594CT[2] U43746.1:n.5950_5951delCT - Protein change
- L1908fs
- Other names
- 5946delCT
- 5950_5951delCT
- 5950delCT
- Canonical SPDI
- NC_000013.11:32340072:CTCTCT:CTCT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- loss_of_function_variant Sequence Ontology [SO:0002054]
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18935 | 19094 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (14) |
reviewed by expert panel
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Apr 22, 2016 | RCV000009905.37 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jan 18, 2024 | RCV000044728.37 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Apr 4, 2023 | RCV000131120.21 | |
Pathogenic (11) |
criteria provided, multiple submitters, no conflicts
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Jul 31, 2024 | RCV000160297.52 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 21, 2024 | RCV000461157.12 | |
Pathogenic (2) |
criteria provided, single submitter
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Jun 23, 2023 | RCV000735574.13 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 2, 2020 | RCV001310125.10 | |
Pathogenic (1) |
no assertion criteria provided
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Jul 1, 2021 | RCV003162224.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 2, 2021 | RCV002496315.8 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Apr 22, 2016)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282413.1
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
(Apr 18, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001450048.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 2
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Pathogenic
(Apr 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499673.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Pathogenic
(Apr 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001572444.1
First in ClinVar: May 01, 2021 Last updated: May 01, 2021 |
Comment:
Variant summary: BRCA2 c.5722_5723delCT (p.Leu1908ArgfsX2) 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.5722_5723delCT (p.Leu1908ArgfsX2) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250888 control chromosomes. c.5722_5723delCT has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple clinical diagnostic laboratories, an expert panel (ENIGMA) and a consortium (CIMBA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jul 01, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
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Department of Medical Genetics, Oslo University Hospital
Accession: SCV000605675.3
First in ClinVar: Sep 30, 2017 Last updated: Dec 11, 2022 |
Number of individuals with the variant: 23
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Pathogenic
(Oct 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002016831.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jun 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000219360.6 First in ClinVar: Mar 29, 2015 Last updated: Feb 04, 2024 |
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Pathogenic
(Apr 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000683728.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 2 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known … (more)
This variant deletes 2 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 5950delCT, 5946delCT and 5950-5951delCT in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least 12 individuals affected with breast and/or ovarian cancer (PMID: 8665505, 14647210, 19353265, 20683152, 21324516, 24010542, 25136594, 26026974, 27553291, 28724667, 29470806, 30287823, 33471991; Leiden Open Variation Database DB-ID BRCA2_001607) and five individuals affected with pancreatic cancer (PMID: 24963353, 25940717) or prostate cancer (PMID: 20736950, 31214711). This variant also has been reported in families suspected of being affected with hereditary breast and ovarian cancer (PMID: 8524414, 11802209, 15340362, 16234499, 25863477). This variant has been identified in 1/250888 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jan 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000072741.16
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Leu1908Argfs*2) 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.Leu1908Argfs*2) 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 (rs80359530, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 8524414, 20736950, 20927582, 21324516, 22535016, 23028338, 24963353, 25940717, 27553291). It has also been observed to segregate with disease in related individuals. This variant is also known as 5950delCT. ClinVar contains an entry for this variant (Variation ID: 9320). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000271330.5
First in ClinVar: May 29, 2016 Last updated: Apr 20, 2024 |
Comment:
The p.Leu1908ArgfsX2 variant in BRCA2 has been reported in >60 individuals with BRCA2-associated cancers (Kwong 2009 PMID: 19353265, Cherbal 2010 PMID: 20683152, Zhang 2011, Edwards … (more)
The p.Leu1908ArgfsX2 variant in BRCA2 has been reported in >60 individuals with BRCA2-associated cancers (Kwong 2009 PMID: 19353265, Cherbal 2010 PMID: 20683152, Zhang 2011, Edwards 2010 PMID: 20736950, Rebbeck 2018 PMID: 29446198, Breast Cancer Information Core (BIC) database). It has also been identified in 0.003% (1/30598) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org); however, this frequency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1908 and leads to a premature termination codon 2 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in HBOC. Additionally, this variant was classified as pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (Variation ID 9320). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP criteria applied: PVS1, PS4, PM2_Supporting. (less)
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Pathogenic
(May 27, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Accession: SCV005045903.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
Comment:
PVS1; PM5_PTC_Strong
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Pathogenic
(Jul 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001501473.21
First in ClinVar: Mar 14, 2021 Last updated: Aug 04, 2024 |
Comment:
BRCA2: PVS1, PM2, PS4:Moderate
Number of individuals with the variant: 5
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Pathogenic
(Nov 03, 2014)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
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Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000195991.1
First in ClinVar: Nov 19, 2015 Last updated: Nov 19, 2015 |
Tissue: Blood
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Pathogenic
(May 04, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000225178.5
First in ClinVar: Jun 28, 2015 Last updated: Sep 28, 2017 |
Number of individuals with the variant: 2
Sex: mixed
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Pathogenic
(Oct 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial breast-ovarian cancer 2
Affected status: unknown
Allele origin:
germline
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Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001434852.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
This c.5722_5723del (p.Leu1908Argfs*2) variant in the BRCA2 gene is predicted to introduce a premature translation termination codon. This variant has been reported in multiple unrelated … (more)
This c.5722_5723del (p.Leu1908Argfs*2) variant in the BRCA2 gene is predicted to introduce a premature translation termination codon. This variant has been reported in multiple unrelated individuals with breast cancer or ovarian cancer (PMID 8524414, 20927582, 21324516, 24010542, 25863477, 27553291), pancreatic cancer (PMID 25940717) and prostate cancer (PMID 20736950). This variant is extremely rare in general population database. Therefore, this c.5722_5723del (p.Leu1908Argfs*2) variant in the BRCA2 gene is classified as pathogenic. (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal unknown)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447288.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Breast carcinoma (present)
Sex: female
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
University of Science and Technology Houari Boumediene, Laboratory of Molecular and Cellular Biology (LBCM)
Accession: SCV002104287.2
First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 2022 |
Age: 30-39 years
Sex: female
Geographic origin: Algeria
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Pathogenic
(Feb 16, 2022)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002536167.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA2 c.5722_5723delCT (p.L1908RfsX2) variant has been reported in heterozygosity in numerous individuals with hereditary breast and/or ovarian cancer (PMID: 33471991, 23028338, 20927582, 21324516, 34026625). … (more)
The BRCA2 c.5722_5723delCT (p.L1908RfsX2) variant has been reported in heterozygosity in numerous individuals with hereditary breast and/or ovarian cancer (PMID: 33471991, 23028338, 20927582, 21324516, 34026625). This variant has also been reported in individuals with prostate or pancreatic cancers (PMID: 27989354, 25940717). It is also known as c.5950delCT in the literature. This variant causes a frameshift at amino acid 1908 that results in premature termination 2 amino acids downstream. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants in BRCA2 are known to be pathogenic (PMID: 29446198). This variant was observed in 1/250888 chromosomes across the different populations included in the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID: 9320). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000327270.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(May 27, 2015)
|
criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000677689.2
First in ClinVar: Jan 06, 2018 Last updated: Dec 24, 2022 |
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Pathogenic
(Nov 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Medulloblastoma Familial prostate cancer Wilms tumor 1 Fanconi anemia complementation group D1 Breast-ovarian cancer, familial, susceptibility to, 2 Glioma susceptibility 3 Pancreatic cancer, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002809681.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Apr 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV003800108.3
First in ClinVar: Feb 13, 2023 Last updated: Jun 10, 2023 |
Comment:
The BRCA2 c.5722_5723delCT; p.Leu1908ArgfsTer2 variant (rs80359530), also known as 5950delCT, has been described in several individuals and families affected with breast, ovarian, prostate, or pancreatic … (more)
The BRCA2 c.5722_5723delCT; p.Leu1908ArgfsTer2 variant (rs80359530), also known as 5950delCT, has been described in several individuals and families affected with breast, ovarian, prostate, or pancreatic cancers (Cherbal 2010, de Juan 2015, Ding 2011, Edwards 2010, Holter 2015, Kwong 2009, Thompson 2012, Zhang 2011). This variant is reported in ClinVar (Variation ID: 9320) and is classified as pathogenic by an expert panel. This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting 2 nucleotides, 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 pathogenic. REFERENCES Cherbal F et al. BRCA1 and BRCA2 germline mutations screening in Algerian breast/ovarian cancer families. Dis Markers. 2010;28(6):377-84. PMID: 20683152. de Juan I et al. BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study. Fam Cancer. 2015 Dec;14(4):505-13. PMID: 26026974. Ding Y et al. Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. Breast Cancer Res Treat. 2011 Apr;126(3):771-8. PMID: 20927582. Edwards S et al. Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis. Br J Cancer. 2010 Sep 7;103(6):918-24. PMID: 20736950. Holter S et al. Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma. J Clin Oncol. 2015 Oct 1;33(28):3124-9. PMID: 25940717. Kwong A et al. A BRCA2 founder mutation and seven novel deleterious BRCA mutations in southern Chinese women with breast and ovarian cancer. Breast Cancer Res Treat. 2009 Oct;117(3):683-6. PMID: 19353265. Thompson E et al. Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. PLoS Genet. 2012 Sep;8(9):e1002894. PMID: 23028338. Zhang S et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol. 2011 May 1;121(2):353-7. PMID: 21324516. (less)
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Pathogenic
(Dec 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210768.16
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
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; Observed … (more)
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; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Wooster 1995, Frank 1998, Couch 2007, Cherbal 2010, de Juan 2015, Holter 2015, Johns 2017, Pritzlaff 2017); Not observed at a significant frequency in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as c.5950delCT; This variant is associated with the following publications: (PMID: 21324516, 20736950, 25136594, 17301269, 19353265, 28008555, 27553291, 29339979, 29335924, 29752822, 22535016, 20683152, 12181777, 26026974, 24830819, 23028338, 9667259, 17453335, 20104584, 22798144, 16835750, 12112655, 12048272, 14973102, 25863477, 8524414, 25940717, 27836010, 26843898, 25330149, 28454591, 27989354, 29470806, 28724667, 30720863, 30940775, 30078507, 30287823, 30720243, 30702160, 31528241, 31577767, 31447099, 31980526) (less)
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Pathogenic
(Oct 25, 2022)
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criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Eurofins-Biomnis
Accession: SCV003935057.1
First in ClinVar: Jun 24, 2023 Last updated: Jun 24, 2023 |
|
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Pathogenic
(Jun 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296745.7
First in ClinVar: Jun 24, 2016 Last updated: Jan 06, 2024 |
Comment:
The BRCA2 c.5722_5723del (p.Leu1908Argfs*2) variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant … (more)
The BRCA2 c.5722_5723del (p.Leu1908Argfs*2) variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in individuals with breast and/or ovarian cancer (PMID: 30940775 (2019), 32341426 (2020), 34290354 (2021)), including male individuals with breast cancer (PMID: 20927582 (2011), 23028338 (2012)). This variant has also been reported in individuals with prostate cancer (PMID: 20736950 (2010)), and pancreatic cancer (PMID: 25940717 (2015), 31577767 (2019)). The frequency of this variant in the general population, 0.000004 (1/250888 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Dec 15, 2023)
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criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004846633.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This variant deletes 2 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known … (more)
This variant deletes 2 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 5950delCT, 5946delCT and 5950-5951delCT in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least 12 individuals affected with breast and/or ovarian cancer (PMID: 8665505, 14647210, 19353265, 20683152, 21324516, 24010542, 25136594, 26026974, 27553291, 28724667, 29470806, 30287823, 33471991; Leiden Open Variation Database DB-ID BRCA2_001607) and five individuals affected with pancreatic cancer (PMID: 24963353, 25940717) or prostate cancer (PMID: 20736950, 31214711). This variant also has been reported in families suspected of being affected with hereditary breast and ovarian cancer (PMID: 8524414, 11802209, 15340362, 16234499, 25863477). This variant has been identified in 1/250888 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
Number of individuals with the variant: 8
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Pathogenic
(Feb 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186050.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.5722_5723delCT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 5722 to … (more)
The c.5722_5723delCT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 5722 to 5723, causing a translational frameshift with a predicted alternate stop codon (p.L1908Rfs*2). This mutation has been reported in multiple hereditary breast and ovarian cancer (HBOC) syndrome cohorts, including individuals with male breast cancer, pancreatic cancer and prostate cancer (Wooster R et al. Nature. 1995 Dec;378:789-92; Edwards SM et al. Br. J. Cancer. 2010 Sep;103:918-24; Cherbal F et al. Dis Markers, 2010;28:377-84; Ding YC et al. Breast Cancer Res. Treat. 2011 Apr;126:771-8; Zhang S et al. Gynecol. Oncol. 2011 May;121(2):353-7; Konstantopoulou I et al. Clin. Genet. 2014 Jan;85:36-42; Johns AL et al. Genome Med. 2014 May;6:42; Ruiz A et al. Biomed Res Int. 2014 Jun;2014:542541; Kang E et al. Breast Cancer Res. Treat. 2015 May;151:157-68; Holter S et al. J. Clin. Oncol. 2015 Oct;33:3124-9; de Juan I et al. Fam. Cancer. 2015 Dec;14:505-13; Rashid MU et al. BMC Cancer. 2016 08;16:673; Na R et al. Eur Urol, 2017 05;71:740-747; Sun J et al. Clin. Cancer Res. 2017 Oct;23:6113-6119; Singh J et al. Breast Cancer Res Treat, 2018 Jul;170:189-196; Momozowa Y et al. Nat Commun. 2018 10;9(1):4083; Wang H et al. Medicine (Baltimore), 2019 Oct;98:e17443; Guo Y et al. Biosci Rep, 2019 04;39; Deng M et al. Int J Cancer, 2019 09;145:1517-1528; De Talhouet S et al. Sci Rep, 2020 04;10:7073; Shao D et al. Cancer Sci, 2020 Feb;111:647-657; Abdel-Razeq H et al. Sci Rep, 2021 07;11:14906). Of note, this mutation is also designated as 5950delCT and c.5718_5719del 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)
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Pathogenic
(Mar 21, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV000541000.2
First in ClinVar: Apr 17, 2017 Last updated: Jun 17, 2024 |
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Pathogenic
(Jul 02, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Department of Human Genetics, Hannover Medical School
Accession: SCV005068269.1
First in ClinVar: Jul 07, 2024 Last updated: Jul 07, 2024 |
Clinical Features:
Breast carcinoma (present)
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Pathogenic
(Jul 31, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV005090043.1
First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024 |
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Pathogenic
(Feb 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199519.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Pathogenic
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline,
somatic,
unknown
|
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000146677.2
First in ClinVar: Apr 01, 2014 Last updated: Nov 19, 2015 |
Observation 1:
Number of individuals with the variant: 16
Observation 2:
Number of individuals with the variant: 2
Geographic origin: Western European
Observation 3:
Number of individuals with the variant: 2
Ethnicity/Population group: Ashkenazi
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Asian, Indian
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Czech Republic
Observation 6:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian Non Hispanic
Observation 8:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 9:
Number of individuals with the variant: 1
Ethnicity/Population group: Latin American, Caribbean
Observation 10:
Number of individuals with the variant: 14
Ethnicity/Population group: Western European
Observation 11:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Italian
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Chinese
Geographic origin: Hksar
Observation 13:
Number of individuals with the variant: 1
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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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: SCV000587796.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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Pathogenic
(May 15, 2015)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863712.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
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: SCV000591992.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Leu1908ArgfsX2 deletion variant has been previously reported in the literature in at least 4 of 3460 proband chromosomes in individuals with hereditary breast, ovarian … (more)
The p.Leu1908ArgfsX2 deletion variant has been previously reported in the literature in at least 4 of 3460 proband chromosomes in individuals with hereditary breast, ovarian or pancreatic cancer and was shown to segregate with disease in one family (Selected publications: Edwards 2010, Heidemann 2012, Kwong 2009, Zhang 2011). In addition, it was reported 17x in the UMD database as causal and 42X in the BIC database as having clinical importance. This DNA alteration leads to a premature stop codon at position 1908, which is predicted to lead to 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. In summary, this variant is classified as pathogenic. (less)
Number of individuals with the variant: 6
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Pathogenic
(Dec 21, 1995)
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no assertion criteria provided
Method: literature only
|
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000030126.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 26, 2015 |
Comment on evidence:
In a family with breast-ovarian cancer (BROVCA2; 612555), Wooster et al. (1995) found a CT deletion which had arisen within a short repetitive sequence: CTCTCT. … (more)
In a family with breast-ovarian cancer (BROVCA2; 612555), Wooster et al. (1995) found a CT deletion which had arisen within a short repetitive sequence: CTCTCT. This feature is characteristic of deletion/insertion mutations in many genes and is presumed to be due to slippage during DNA synthesis. (less)
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Pathogenic
(Mar 28, 2013)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000054177.6
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2016 |
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Pathogenic
(-)
|
no assertion criteria provided
Method: literature only
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Center for Precision Medicine, Meizhou People's Hospital
Accession: SCV002520809.1
First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022 |
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Pathogenic
(Aug 26, 2022)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV002588891.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
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Pathogenic
(Jul 01, 2021)
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no assertion criteria provided
Method: research
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Gastric cancer
Affected status: unknown
Allele origin:
germline
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Laboratory for Genotyping Development, RIKEN
Accession: SCV002758433.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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loss_of_function_variant
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University of Science and Technology Houari Boumediene, Laboratory of Molecular and Cellular Biology (LBCM)
Accession: SCV002104287.2
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
Prevalence and predictors of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan. | Abdel-Razeq H | Scientific reports | 2021 | PMID: 34290354 |
Exome sequencing in BRCA1-2 candidate familias: the contribution of other cancer susceptibility genes. | Doddato G | Frontiers in oncology | 2021 | PMID: 34026625 |
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. | De Talhouet S | Scientific reports | 2020 | PMID: 32341426 |
Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals. | Shao D | Cancer science | 2020 | PMID: 31742824 |
Germline Pathogenic Variants in 7636 Japanese Patients With Prostate Cancer and 12 366 Controls. | Momozawa Y | Journal of the National Cancer Institute | 2020 | PMID: 31214711 |
A case report of a dramatic response to olaparib in a patient with metastatic pancreatic cancer harboring a germline BRCA2 mutation. | Wang H | Medicine | 2019 | PMID: 31577767 |
Identifying a BRCA2 c.5722_5723del mutation in a Han-Chinese family with breast cancer. | Guo Y | Bioscience reports | 2019 | PMID: 30940775 |
Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China. | Deng M | International journal of cancer | 2019 | PMID: 30720863 |
Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations. | Singh J | Breast cancer research and treatment | 2018 | PMID: 29470806 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
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 |
High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients. | Rashid MU | BMC cancer | 2016 | PMID: 27553291 |
BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study. | de Juan I | Familial cancer | 2015 | PMID: 26026974 |
Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma. | Holter S | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2015 | PMID: 25940717 |
The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study. | Kang E | Breast cancer research and treatment | 2015 | PMID: 25863477 |
Genetic testing in hereditary breast and ovarian cancer using massive parallel sequencing. | Ruiz A | BioMed research international | 2014 | PMID: 25136594 |
Returning individual research results for genome sequences of pancreatic cancer. | Johns AL | Genome medicine | 2014 | PMID: 24963353 |
High prevalence of BRCA1 founder mutations in Greek breast/ovarian families. | Konstantopoulou I | Clinical genetics | 2014 | PMID: 24010542 |
BRCA1 and BRCA2 germline mutation spectrum in hereditary breast/ovarian cancer families from Maghrebian countries. | Cherbal F | Breast disease | 2012 | PMID: 23697973 |
Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. | Thompson ER | PLoS genetics | 2012 | PMID: 23028338 |
Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. | Kim H | Breast cancer research and treatment | 2012 | PMID: 22798144 |
Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management. | Heidemann S | Breast cancer research and treatment | 2012 | PMID: 22535016 |
Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. | Zhang S | Gynecologic oncology | 2011 | PMID: 21324516 |
Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. | Ding YC | Breast cancer research and treatment | 2011 | PMID: 20927582 |
Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis. | Edwards SM | British journal of cancer | 2010 | PMID: 20736950 |
BRCA1 and BRCA2 germline mutations screening in Algerian breast/ovarian cancer families. | Cherbal F | Disease markers | 2010 | PMID: 20683152 |
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 |
A BRCA2 founder mutation and seven novel deleterious BRCA mutations in southern Chinese women with breast and ovarian cancer. | Kwong A | Breast cancer research and treatment | 2009 | PMID: 19353265 |
Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. | Risch HA | Journal of the National Cancer Institute | 2006 | PMID: 17148771 |
[Mutational analysis of BRCA1 and BRCA2 genes in early-onset breast cancer patients in Shanghai]. | Song CG | Zhonghua yi xue za zhi | 2005 | PMID: 16324400 |
Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. | Nanda R | JAMA | 2005 | PMID: 16234499 |
Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations. | Marroni F | European journal of human genetics : EJHG | 2004 | PMID: 15340362 |
A high frequency of BRCA2 gene mutations in Polish families with ovarian and stomach cancer. | Jakubowska A | European journal of human genetics : EJHG | 2003 | PMID: 14647210 |
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. | Meindl A | International journal of cancer | 2002 | PMID: 11802209 |
Mutations of the BRCA2 gene in ovarian carcinomas. | Takahashi H | Cancer research | 1996 | PMID: 8665505 |
Identification of the breast cancer susceptibility gene BRCA2. | Wooster R | Nature | 1995 | PMID: 8524414 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2 | - | - | - | - |
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Text-mined citations for rs80359530 ...
HelpRecord last updated Aug 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.