Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000113219 | SCV000282383 | pathogenic | Breast-ovarian cancer, familial 2 | 2016-04-22 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
Invitae | RCV000044266 | SCV000072279 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2019-10-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser1262*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80358620, ExAC 0.002%). This variant has been observed in an individual affected with ovarian cancer (PMID: 24728189). ClinVar contains an entry for this variant (Variation ID: 51525). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000129108 | SCV000183819 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-01-07 | criteria provided, single submitter | clinical testing | Alterations resulting in premature truncation (e.g.reading frame shift, nonsense) |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000113219 | SCV000326915 | pathogenic | Breast-ovarian cancer, familial 2 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000481804 | SCV000566129 | pathogenic | not provided | 2018-11-26 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.3785C>G at the cDNA level and p.Ser1262Ter (S1262X) at the protein level. Using alternate nomenclature, this variant would be defined as 4013C>G. 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. This variant has been reported in association with breast and ovarian cancer (Loughrey 2008, de Juan Jim?nez 2013, Song 2014). We consider this variant to be pathogenic. |
Counsyl | RCV000113219 | SCV000786273 | pathogenic | Breast-ovarian cancer, familial 2 | 2018-04-02 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000044266 | SCV000916867 | pathogenic | Hereditary breast and ovarian cancer syndrome | 2020-09-03 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.3785C>G (p.Ser1262X) 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 allele was found at a frequency of 4.1e-06 in 245754 control chromosomes (gnomAD and publication data). c.3785C>G has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Coulet_2010, Song_2014, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten ClinVar submitters (evaluation after 2014), including one expert panel (ENIGMA), cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Hudson |
RCV000113219 | SCV000993559 | pathogenic | Breast-ovarian cancer, familial 2 | 2019-05-23 | criteria provided, single submitter | research | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000481804 | SCV001133771 | pathogenic | not provided | 2019-02-22 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity. |
Color | RCV000129108 | SCV001340013 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-12-04 | criteria provided, single submitter | clinical testing | |
Breast Cancer Information Core |
RCV000113219 | SCV000146297 | pathogenic | Breast-ovarian cancer, familial 2 | no assertion criteria provided | clinical testing | ||
Sharing Clinical Reports Project |
RCV000113219 | SCV000297522 | pathogenic | Breast-ovarian cancer, familial 2 | 2012-04-30 | no assertion criteria provided | clinical testing | |
True Health Diagnostics | RCV000129108 | SCV000805241 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-04-09 | no assertion criteria provided | clinical testing |