ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6768T>A (p.Cys2256Ter)

dbSNP: rs80358901
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Total submissions: 6
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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) RCV000113641 SCV000301107 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 RCV000113641 SCV000327518 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193921 SCV001363095 pathogenic Hereditary breast ovarian cancer syndrome 2019-10-11 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6768T>A (p.Cys2256X) 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 251254 control chromosomes (gnomAD). c.6768T>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (e.g. Rebbeck_2018, Finkelman_2012). These data indicate that the variant may be associated with disease. The variant has also been reported as associated with breast and ovarian cancer in several well known databases (NHGRI_BIC, LOVD). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001193921 SCV001582020 pathogenic Hereditary breast ovarian cancer syndrome 2021-12-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 52180). This premature translational stop signal has been observed in individual(s) with high risk of breast and ovarian cancer (PMID: 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys2256*) 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).
Breast Cancer Information Core (BIC) (BRCA2) RCV000113641 SCV000146928 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2002-06-20 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735590 SCV000863728 pathogenic Breast and/or ovarian cancer 2002-11-25 no assertion criteria provided clinical testing

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