Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017967 | SCV001179137 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-06 | criteria provided, single submitter | clinical testing | The p.E2844G variant (also known as c.8531A>G), located in coding exon 19 of the BRCA2 gene, results from an A to G substitution at nucleotide position 8531. The glutamic acid at codon 2844 is replaced by glycine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with a fallopian tube cancer (Hundal J et al. J Community Hosp Intern Med Perspect, 2021 May;11:393-396). This amino acid position is not 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. |
| Labcorp Genetics |
RCV001050193 | SCV001214289 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-09-26 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 822539). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2844 of the BRCA2 protein (p.Glu2844Gly). |
| Gene |
RCV001759700 | SCV002005017 | uncertain significance | not provided | 2019-08-06 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV003461367 | SCV004216015 | uncertain significance | Familial cancer of breast | 2023-07-17 | criteria provided, single submitter | clinical testing |