Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001957945 | SCV002210838 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-09-18 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with histidine at codon 2712 of the BRCA2 protein (p.Asp2712His). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. 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 | RCV003167421 | SCV003853849 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-26 | criteria provided, single submitter | clinical testing | The p.D2712H variant (also known as c.8134G>C), located in coding exon 17 of the BRCA2 gene, results from a G to C substitution at nucleotide position 8134. The aspartic acid at codon 2712 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. 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. |