Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000572915 | SCV000668789 | likely benign | Hereditary cancer-predisposing syndrome | 2017-04-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV001230752 | SCV001403243 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-01-12 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 2452 of the BRCA2 protein (p.Asn2452Ser). This variant is present in population databases (rs398122581, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 91476). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV002509201 | SCV002818835 | uncertain significance | not provided | 2022-12-30 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 7583A>G; This variant is associated with the following publications: (PMID: 29884841, 32377563) |
| Sharing Clinical Reports Project |
RCV000076993 | SCV000108790 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2009-12-14 | no assertion criteria provided | clinical testing |