Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001244683 | SCV001417919 | pathogenic | Hereditary breast ovarian cancer syndrome | 2021-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu2139Cysfs*29) 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001244683 | SCV002766415 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2022-11-03 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.6415_6426delins11 (p.Glu2139CysfsX29) 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 population databases (gnomAD), however the technology used in such databases may not be able to detect variants of this type. To our knowledge, no occurrence of c.6415_6426delins11 in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |