Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000579812 | SCV000683982 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-17 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 2850 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals undergoing BRCA mutation testing (PMID: 30675319). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV001857376 | SCV002237439 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-11-23 | 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: 52619). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2850 of the BRCA2 protein (p.Glu2850Lys). |
| Ambry Genetics | RCV000579812 | SCV005030937 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-06 | criteria provided, single submitter | clinical testing | The p.E2850K variant (also known as c.8548G>A), located in coding exon 19 of the BRCA2 gene, results from a G to A substitution at nucleotide position 8548. The glutamic acid at codon 2850 is replaced by lysine, an amino acid with 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 alteration remains unclear. |
| Breast Cancer Information Core |
RCV000113959 | SCV000147399 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2004-02-20 | no assertion criteria provided | clinical testing |