Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000524906 | SCV000635652 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 2765 of the BRCA2 protein (p.Cys2765Arg). 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: 462474). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA2 protein function. 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. |
| Mendelics | RCV000524906 | SCV000838872 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000989070 | SCV001139211 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002431581 | SCV002679260 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-26 | criteria provided, single submitter | clinical testing | The p.C2765R variant (also known as c.8293T>C), located in coding exon 17 of the BRCA2 gene, results from a T to C substitution at nucleotide position 8293. The cysteine at codon 2765 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |