Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000562924 | SCV000661263 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-27 | criteria provided, single submitter | clinical testing | The p.G2919D variant (also known as c.8756G>A), located in coding exon 21 of the BRCA2 gene, results from a G to A substitution at nucleotide position 8756. The glycine at codon 2919 is replaced by aspartic acid, an amino acid with similar properties. This alteration was identified in an individual diagnosed with prostate cancer (Mondschein R et al. Cancers (Basel), 2022 Jul;14:). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001041363 | SCV001204974 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2919 of the BRCA2 protein (p.Gly2919Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 35892882). ClinVar contains an entry for this variant (Variation ID: 479303). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284592 | SCV001470455 | uncertain significance | not provided | 2020-03-20 | criteria provided, single submitter | clinical testing |