Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000687901 | SCV000815493 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-05-15 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs757824441, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 3080 of the BRCA2 protein (p.Ser3080Cys). 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: 567735). 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. 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. |
| Color Diagnostics, |
RCV001188321 | SCV001355349 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-10 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001188321 | SCV002687936 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-03 | criteria provided, single submitter | clinical testing | The p.S3080C variant (also known as c.9239C>G), located in coding exon 23 of the BRCA2 gene, results from a C to G substitution at nucleotide position 9239. The serine at codon 3080 is replaced by cysteine, an amino acid with 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. |
| Gene |
RCV004588109 | SCV005078505 | uncertain significance | not provided | 2024-05-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates 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 9467C>G; This variant is associated with the following publications: (PMID: 31131967, 12228710) |
| All of Us Research Program, |
RCV004802359 | SCV005425837 | uncertain significance | BRCA2-related cancer predisposition | 2024-05-14 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with cysteine at codon 3080 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a multifactorial analysis with co-occurrence and family history likelihood ratios for pathogenicity of 1.0498 and 0.492, respectively (PMID: 31131967). This variant has been identified in 2/250310 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. |