Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000773274 | SCV000906951 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-02 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 2800 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). A functional study has reported that this variant has no impact on BRCA2 function in a homology-directed repair assay (PMID: 29884841). This variant has been reported in an individual affected with prostate cancer (PMID: 31214711). 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 |
RCV001857375 | SCV002221111 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-02-28 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 2800 of the BRCA2 protein (p.Pro2800Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 52576). Experimental studies have shown that this variant does not substantially affect BRCA2 protein 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. |
| Center for Genomic Medicine, |
RCV002267817 | SCV002551817 | uncertain significance | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000773274 | SCV002677728 | likely benign | Hereditary cancer-predisposing syndrome | 2020-02-12 | 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. |
| All of Us Research Program, |
RCV004803911 | SCV005425794 | uncertain significance | BRCA2-related cancer predisposition | 2024-03-05 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 2800 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). A functional study has reported that this variant has no impact on BRCA2 function in a homology-directed repair assay (PMID: 29884841). This variant has been reported in an individual affected with prostate cancer (PMID: 31214711). 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. |
| Breast Cancer Information Core |
RCV000113926 | SCV000147355 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2007-01-18 | no assertion criteria provided | clinical testing |