Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564997 | SCV000666031 | likely benign | Hereditary cancer-predisposing syndrome | 2020-02-26 | 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. |
| Color Diagnostics, |
RCV000564997 | SCV000683915 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-06 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with alanine at codon 2639 of the BRCA2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown this variant does not impact homology-directed DNA repair (PMID: 29394989, 35736817). This variant has been reported in an unaffected individual (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_000240) and in a multifactorial analysis with family history, pathology, and co-segregation likelihood ratios for pathogenicity of 0.15, 0.61, and 0.03, respectively (PMID: 34597585). This variant has not been identified 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. |
| Labcorp Genetics |
RCV001363807 | SCV001559934 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2639 of the BRCA2 protein (p.Pro2639Ala). This variant is not present in population databases (gnomAD no frequency). 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: 52434). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33609447) indicates that this missense variant is not expected to disrupt BRCA2 function. Experimental studies have shown that this missense change does not substantially affect BRCA2 function (PMID: 29394989). 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. |
| Sema4, |
RCV000564997 | SCV002531891 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-01 | criteria provided, single submitter | curation | |
| Baylor Genetics | RCV003460614 | SCV004216058 | uncertain significance | Familial cancer of breast | 2023-06-29 | criteria provided, single submitter | clinical testing | |
| Breast Cancer Information Core |
RCV000113838 | SCV000147215 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
| Sharing Clinical Reports Project |
RCV000113838 | SCV000297555 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2008-08-04 | no assertion criteria provided | clinical testing |