Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002658120 | SCV002974333 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 2819 of the BRCA2 protein (p.Asp2819Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 31954625). 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. |
| Ambry Genetics | RCV004603215 | SCV005102047 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-01 | criteria provided, single submitter | clinical testing | The p.D2819E variant (also known as c.8457T>A), located in coding exon 18 of the BRCA2 gene, results from a T to A substitution at nucleotide position 8457. The aspartic acid at codon 2819 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |