ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7133C>G (p.Ser2378Ter) (rs276174889)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216056 SCV000275488 pathogenic Hereditary cancer-predisposing syndrome 2017-09-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031667 SCV000147028 pathogenic Breast-ovarian cancer, familial 2 2010-09-18 no assertion criteria provided clinical testing
Color RCV000216056 SCV000683854 pathogenic Hereditary cancer-predisposing syndrome 2015-04-13 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031667 SCV000327596 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031667 SCV000282440 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000478738 SCV000568481 pathogenic not provided 2018-04-09 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7133C>G at the cDNA level and p.Ser2378Ter (S2378X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Using alternate nomenclature, this variant would be defined as BRCA2 7361C>G. This variant was identified in a high-risk breast and/or ovarian cancer patient (Kwong 2016). Based on currently available evidence, we consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000045148 SCV000695041 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-04 criteria provided, single submitter clinical testing Variant summary: The c.7133C>G (p.Ser2378*) in BRCA2 gene is gene is a nonsense change predicted cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. The variant is absent from the large control population datasets of ExAC and gnomAD (0/121342 and 0/245968 chrs tested, respectively). The variant has been reported in several affected individuals with personal and/or family history of cancer. In addition, multiple reputable databases/clinical laboratories cite the variant as Pathogenic. Taking together, the variant of interest was classified as Pathogenic.
Invitae RCV000045148 SCV000073161 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser2378*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with breast and/or ovarian cancer (PMID: 27157322) and in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 38085). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031667 SCV000054274 pathogenic Breast-ovarian cancer, familial 2 2011-06-28 no assertion criteria provided clinical testing

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