ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2214T>A (p.Cys738Ter)

dbSNP: rs398122742
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077679 SCV000300497 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077679 SCV000326672 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000581800 SCV000688747 pathogenic Hereditary cancer-predisposing syndrome 2021-09-03 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000693161 SCV000821017 pathogenic Hereditary breast ovarian cancer syndrome 2021-05-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has been reported in individuals with personal and/or family history of breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 91771). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys738*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product.
GeneDx RCV001588902 SCV001825790 pathogenic not provided 2020-01-22 criteria provided, single submitter clinical testing 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; Observed in individuals evaluated for hereditary breast and ovarian cancer (Rebbeck 2018); 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); Also known as 2442T>A; This variant is associated with the following publications: (PMID: 29446198)
Ambry Genetics RCV000581800 SCV002730836 pathogenic Hereditary cancer-predisposing syndrome 2024-01-02 criteria provided, single submitter clinical testing The p.C738* pathogenic mutation (also known as c.2214T>A), located in coding exon 10 of the BRCA2 gene, results from a T to A substitution at nucleotide position 2214. This changes the amino acid from a cysteine to a stop codon within coding exon 10. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001588902 SCV004562582 pathogenic not provided 2023-09-26 criteria provided, single submitter clinical testing The BRCA2 c.2214T>A; p.Cys738Ter variant (rs398122742) is reported in the literature in individuals with a personal or family history of breast and/or ovarian cancer (Rebbeck 2018). This variant is reported in ClinVar (Variation ID: 91771), and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Rebbeck TR et al. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat. 2018 May;39(5):593-620. PMID: 29446198.
Fulgent Genetics, Fulgent Genetics RCV005007990 SCV005633888 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Familial prostate cancer 2024-04-19 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077679 SCV000109482 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2012-05-01 no assertion criteria provided clinical testing

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