ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.5238dup (p.Asn1747Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.5238dup (p.Asn1747Ter)
Variation ID: 37954 Accession: VCV000037954.91
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32339592-32339593 (GRCh38) [ NCBI UCSC ] 13: 32913730 (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 1, 2014 May 1, 2024 Sep 8, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.5238dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Asn1747Ter nonsense NM_000059.3:c.5238dupT NC_000013.11:g.32339593dup NC_000013.10:g.32913730dup NG_012772.3:g.29114dup LRG_293:g.29114dup U43746.1:n.5466_5467insT - Protein change
- N1747*
- Other names
- 5466insT
- Canonical SPDI
- NC_000013.11:32339592:T:TT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
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
Help
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 |
18723 | 18881 |
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 (8) |
reviewed by expert panel
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Sep 8, 2016 | RCV000031535.23 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Feb 6, 2023 | RCV000130726.20 | |
Pathogenic (10) |
criteria provided, multiple submitters, no conflicts
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Feb 6, 2024 | RCV000212240.34 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2024 | RCV000257922.26 | |
Pathogenic (1) |
no assertion criteria provided
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- | RCV001353486.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 14, 2024 | RCV003884336.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 13, 2024 | RCV003924877.1 | |
Pathogenic (2) |
criteria provided, single submitter
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Nov 17, 2021 | RCV001170969.13 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jul 24, 2023 | RCV001262734.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 16, 2022 | RCV002496483.8 |
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
(Sep 08, 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: SCV000300851.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Nov 06, 2015)
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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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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000219349.3 First in ClinVar: Mar 29, 2015 Last updated: Aug 27, 2017 |
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Pathogenic
(Jan 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: no
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440711.1
First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020 |
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Pathogenic
(Sep 22, 2017)
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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: SCV001449908.1
First in ClinVar: Dec 10, 2020 Last updated: Dec 10, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(Dec 07, 2020)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001716155.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Comment:
PVS1, PM2, PP5
Number of individuals with the variant: 1
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Pathogenic
(Jun 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762063.1
First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021 |
Clinical Features:
Pancreatic adenocarcinoma (present)
Sex: female
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Pathogenic
(Jan 26, 2021)
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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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GeneDx
Accession: SCV000210763.9
First in ClinVar: Feb 24, 2015 Last updated: Apr 17, 2019 |
Comment:
Nonsense 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; Reported … (more)
Nonsense 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; Reported in association with hereditary breast and/or ovarian cancer (Frank 1998, Meindl 2002, Nanda 2005, Pohlreich 2005, van der Hout 2006, Song 2014, Wong-Brown 2015, Frey 2017); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 24504028, 24728189, 26681312, 27856273, 28495237, 28324225, 32295079, 16168118, 18703817, 22430266, 16234499, 15131399, 16683254, 9667259, 23110154, 27157322, 25682074, 11802209, 28454591, 27930734, 26022348, 30702160, 32719484) (less)
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Pathogenic
(Jun 20, 2022)
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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: SCV000694848.2
First in ClinVar: Dec 26, 2017 Last updated: Aug 08, 2022 |
Comment:
Variant summary: BRCA2 c.5238dupT (p.Asn1747X) 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.5238dupT (p.Asn1747X) 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 was absent in 252034 control chromosomes. c.5238dupT has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Meindl_2002, Nanda_2005, Palma_2008, Pern_2012, Pohlreich_2005, Song_2014). 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 and an expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified 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: SCV000327184.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Dec 28, 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:
unknown
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Counsyl
Accession: SCV000488096.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(Nov 17, 2021)
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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
Accession: SCV001333629.3
First in ClinVar: May 31, 2020 Last updated: Mar 11, 2023 |
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Pathogenic
(Jul 24, 2023)
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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: SCV004213729.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Nov 30, 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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Revvity Omics, Revvity
Accession: SCV002019086.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Feb 06, 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: SCV000905014.4
First in ClinVar: May 19, 2019 Last updated: Feb 14, 2024 |
Comment:
This variant inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least eight individuals affected with breast or ovarian cancer and additional suspected hereditary breast and ovarian cancer families (PMID: 9667259, 11802209, 16168118, 16234499, 18703817, 23110154, 24504028, 24728189, 25186627, 25682074, 26681312). This variant has not been identified 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
(Feb 14, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004698109.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
Comment:
Criteria applied: PVS1,PM5_STR,PM2_SUP
Clinical Features:
Ovarian carcinoma (present) , Neoplasm of the pancreas (present) , Breast carcinoma (present)
Sex: female
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Pathogenic
(Feb 13, 2024)
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criteria provided, single submitter
Method: clinical testing
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BRCA2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004740625.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The BRCA2 c.5238dupT variant is predicted to result in premature protein termination (p.Asn1747*). This variant has been documented to be pathogenic in multiple unrelated individuals … (more)
The BRCA2 c.5238dupT variant is predicted to result in premature protein termination (p.Asn1747*). This variant has been documented to be pathogenic in multiple unrelated individuals with breast or ovarian cancer [Reported in Table III as 5466insT(1747X) in Meindl et al. 2002. PubMed ID: 11802209; reported as c.5238insT in Pern et al. 2012. PubMed ID: 23110154; reported in Table S1 as S1746fs in Cunningham et al. 2014. PubMed ID: 24504028; reported in Suppl Table 1 as c.5237_5238insT (p.S1746fs) in Schroeder et al. 2015. PubMed ID: 26022348]. This variant has not been reported in a large population database, indicating this variant is rare. It is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/37954/). Nonsense variants in BRCA2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Aug 15, 2023)
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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: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004845790.1
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 inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least eight individuals affected with breast or ovarian cancer and additional suspected hereditary breast and ovarian cancer families (PMID: 9667259, 11802209, 16168118, 16234499, 18703817, 23110154, 24504028, 24728189, 25186627, 25682074, 26681312). This variant has not been identified 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: 2
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Pathogenic
(Dec 28, 2021)
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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: SCV000185615.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.5238dupT pathogenic mutation (also known as p.N1747*), located in coding exon 10 of the BRCA2 gene, results from a duplication of T at nucleotide … (more)
The c.5238dupT pathogenic mutation (also known as p.N1747*), located in coding exon 10 of the BRCA2 gene, results from a duplication of T at nucleotide position 5238. This changes the amino acid from a asparagine to a stop codon within coding exon 10. This mutation has been described in multiple breast and/or ovarian cancer families, including individuals with pre-menopausal and triple negative breast cancer (Frank TS et al. J. Clin. Oncol. 1998 Jul;16(7):2417-25; Meindl A et al. Int. J. Cancer. 2002 Feb;97(4):472-80; Pohlreich P et al. Breast Cancer Res. 2005 Jul;7(5):R728-36; Palma MD et al. Cancer Res. 2008 Sep;68(17):7006-14; Pern F et al. PLoS One. 2012 Oct;7(10):e47993; Wong-Brown MW et al. Breast Cancer Res. Treat. 2015 Feb;150:71-80; Schroeder C et al. Breast Cancer Res. Treat. 2015 Jul;152:129-136). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this alteration is also designated as 5466insT 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
(Apr 21, 2016)
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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
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000267778.1
First in ClinVar: Mar 29, 2015 Last updated: Mar 29, 2015 |
Tissue: Blood
|
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Pathogenic
(Apr 20, 2017)
|
criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Department of Pathology and Molecular Medicine, Queen's University
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000588099.1 First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
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Pathogenic
(Jan 16, 2018)
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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
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000747811.1
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
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Pathogenic
(Feb 16, 2022)
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criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Medulloblastoma Malignant tumor of prostate 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: SCV002811039.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010358.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
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Pathogenic
(Aug 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296566.5
First in ClinVar: Mar 29, 2015 Last updated: Jan 06, 2024 |
Comment:
This frameshift variant causes the premature termination of BRCA2 protein synthesis. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In addition, … (more)
This frameshift variant causes the premature termination of BRCA2 protein synthesis. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In addition, it has been described in individuals with breast cancer and ovarian cancer (PMID: 26681312 (2015), 25682074 (2015), 25186627 (2015), 24728189 (2014), 22430266 (2012)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Feb 06, 2024)
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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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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004024414.3
First in ClinVar: Aug 13, 2023 Last updated: Feb 14, 2024 |
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Pathogenic
(Jan 25, 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: SCV000072631.13
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Asn1747*) 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.Asn1747*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 11802209, 16168118, 23110154, 25682074, 26681312). This variant is also known as 5466insT. ClinVar contains an entry for this variant (Variation ID: 37954). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 06, 2011)
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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: SCV000054140.4
First in ClinVar: Apr 04, 2013 Last updated: Mar 29, 2015 |
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Pathogenic
(Jun 11, 2019)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
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CZECANCA consortium
Accession: SCV001451857.1
First in ClinVar: Dec 26, 2020 Last updated: Dec 26, 2020 |
Number of individuals with the variant: 1
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
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: SCV000591954.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The BRCA2 p.Asn1747X variant was identified in 3 of 1936 proband chromosomes (frequency: 0.002) from German and Czech individuals or families with breast/ovarian or triple … (more)
The BRCA2 p.Asn1747X variant was identified in 3 of 1936 proband chromosomes (frequency: 0.002) from German and Czech individuals or families with breast/ovarian or triple negative breast cancers (Meindl 2002, Pohlreich 2005, Pern 2012). The variant was also identified in dbSNP (ID: rs80359499) “With Pathogenic allele”, but no frequency information was provided, thus the prevalence of this variant in the general population could not be determined. The variant was identified in HGMD, the BIC database (9X with pathogenic clinical importance), and in Clinvitae (3x), the ClinVar database by multiple submitters (the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports) as a pathogenic variant, 2X by BIC (both somatic and germline) classification not provided, Invitae, classification not provided, classified as pathogenic by Ambry Genetics, GeneDX and Molecular Diagnostic Laboratory - CHEO ). The c.5238 duplication variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1747 and leads to a premature stop codon at position 1747. 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. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001741278.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001972057.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587753.1 First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
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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: SCV002588883.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
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not provided
(-)
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no classification provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline,
somatic
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Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000146580.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 2
Observation 2:
Number of individuals with the variant: 2
Geographic origin: Western, Central/Eastern European
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian Non Hispanic
Observation 4:
Number of individuals with the variant: 3
Ethnicity/Population group: Western European
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, English, Irish, German
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: Chinese
Geographic origin: Hksar
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program participants. | Murali K | Hereditary cancer in clinical practice | 2021 | PMID: 34399810 |
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 |
Population genetic screening efficiently identifies carriers of autosomal dominant diseases. | Grzymski JJ | Nature medicine | 2020 | PMID: 32719484 |
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 |
Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help? | Zuntini R | Frontiers in genetics | 2018 | PMID: 30254663 |
Analysis of protein-coding genetic variation in 60,706 humans. | Lek M | Nature | 2016 | PMID: 27535533 |
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 |
HBOC multi-gene panel testing: comparison of two sequencing centers. | Schroeder C | Breast cancer research and treatment | 2015 | PMID: 26022348 |
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 |
Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. | Wong-Brown MW | Breast cancer research and treatment | 2015 | PMID: 25682074 |
Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. | Tung N | Cancer | 2015 | PMID: 25186627 |
The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. | Song H | Human molecular genetics | 2014 | PMID: 24728189 |
Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. | Cunningham JM | Scientific reports | 2014 | PMID: 24504028 |
Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospital-based series of German patients with triple-negative breast cancer. | Pern F | PloS one | 2012 | PMID: 23110154 |
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 |
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 |
The relative contribution of point mutations and genomic rearrangements in BRCA1 and BRCA2 in high-risk breast cancer families. | Palma MD | Cancer research | 2008 | PMID: 18703817 |
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 |
High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area. | Pohlreich P | Breast cancer research : BCR | 2005 | PMID: 16168118 |
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 |
Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. | Frank TS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 1998 | PMID: 9667259 |
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Text-mined citations for rs80359499 ...
HelpRecord last updated May 01, 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.