Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130806 | SCV000185702 | uncertain significance | Hereditary cancer-predisposing syndrome | 2013-09-24 | criteria provided, single submitter | clinical testing | The p.E2121K variant (also known as c.6361G>A or 6589G>A) is located in coding exon 10 of the BRCA2 gene. This alteration results from a G to A substitution at nucleotide position 6361. The glutamic acid at codon 2121 is replaced by lysine, an amino acid with similar properties. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. Based on protein sequence alignment, 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. Since supporting evidence is limited at this time, the clinical significance of p.E2121K remains unclear. |
| Invitae | RCV002514737 | SCV003203127 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-06-15 | 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: 142020). 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 2121 of the BRCA2 protein (p.Glu2121Lys). |
| University of Washington Department of Laboratory Medicine, |
RCV000130806 | SCV003852458 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| Research Molecular Genetics Laboratory, |
RCV000496406 | SCV000587836 | uncertain significance | not specified | 2014-01-31 | no assertion criteria provided | research |