Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
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 |
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, |
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 |
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 |
RCV000113641 | SCV000146928 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-06-20 | no assertion criteria provided | clinical testing | |
Foulkes Cancer Genetics LDI, |
RCV000735590 | SCV000863728 | pathogenic | Breast and/or ovarian cancer | 2002-11-25 | no assertion criteria provided | clinical testing |