Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000205206 | SCV000259949 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 99 of the BRCA2 protein (p.Asp99Gly). 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: 219849). 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%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Ambry Genetics | RCV001017701 | SCV001178823 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-02 | criteria provided, single submitter | clinical testing | The p.D99G variant (also known as c.296A>G), located in coding exon 2 of the BRCA2 gene, results from an A to G substitution at nucleotide position 296. The aspartic acid at codon 99 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved and glycine is a reference amino acid in several species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site; however direct evidence is insufficient (Ambry internal data). In addition, as a missense, this alteration is predicted to be tolerated by protein in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Baylor Genetics | RCV003462372 | SCV004216003 | uncertain significance | Familial cancer of breast | 2024-02-02 | criteria provided, single submitter | clinical testing |