Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000559770 | SCV000635599 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-04-27 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 91487). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs41293507, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2550 of the BRCA2 protein (p.Ile2550Val). |
| Color Diagnostics, |
RCV000776374 | SCV000911806 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 2550 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 35864222) and an unaffected individual (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_003369). This variant has been identified in 1/251108 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV000776374 | SCV002670704 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-21 | 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. |
| Gene |
RCV003128579 | SCV003805847 | uncertain significance | not provided | 2022-08-25 | 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 7876A>G; This variant is associated with the following publications: (PMID: 12228710, 31131967) |
| Sharing Clinical Reports Project |
RCV000077004 | SCV000108801 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-02-15 | no assertion criteria provided | clinical testing |