Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000218173 | SCV000273347 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-20 | criteria provided, single submitter | clinical testing | The p.V2908M variant (also known as c.8722G>A), located in coding exon 20 of the BRCA2 gene, results from a G to A substitution at nucleotide position 8722. The valine at codon 2908 is replaced by methionine, an amino acid with highly similar 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. |
| Gene |
RCV000482964 | SCV000567930 | uncertain significance | not provided | 2018-06-21 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.8722G>A at the cDNA level, p.Val2908Met (V2908M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). Using alternate nomenclature, this variant would be defined as BRCA2 8950G>A. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA2 Val2908Met was not observed in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Yang 2002). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Val2908Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV000821493 | SCV000962251 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-02-12 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2908 of the BRCA2 protein (p.Val2908Met). 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: 126188). 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 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. |
| Breast Cancer Information Core |
RCV000113989 | SCV000147443 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-06-27 | no assertion criteria provided | clinical testing |