Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131322 | SCV000186295 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-09 | criteria provided, single submitter | clinical testing | The p.S2358C variant (also known as c.7073C>G), located in coding exon 13 of the BRCA2 gene, results from a C to G substitution at nucleotide position 7073. The serine at codon 2358 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is well 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. |
| Labcorp Genetics |
RCV000701650 | SCV000830461 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2358 of the BRCA2 protein (p.Ser2358Cys). This variant is present in population databases (rs431825349, gnomAD 0.006%). 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: 96847). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800391 | SCV002046757 | uncertain significance | not provided | 2022-09-07 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.000008 (2/250962 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. To the best of our knowledge, the variant has not been reported in individuals with BRC2 related conditions in the published literature. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. |
| Sharing Clinical Reports Project |
RCV000082968 | SCV000115042 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-05-01 | no assertion criteria provided | clinical testing |