Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000221416 | SCV000274207 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-05 | criteria provided, single submitter | clinical testing | The p.L3344V variant (also known as c.10030C>G), located in coding exon 26 of the BRCA2 gene, results from a C to G substitution at nucleotide position 10030. The leucine at codon 3344 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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 this alteration remains unclear. |
| Labcorp Genetics |
RCV000229862 | SCV000283159 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3344 of the BRCA2 protein (p.Leu3344Val). This variant is present in population databases (rs377155248, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 230604). 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 with a negative predictive value of 95%. 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 | RCV004998449 | SCV005624307 | uncertain significance | not provided | 2024-11-08 | criteria provided, single submitter | clinical testing | The BRCA2 c.10030C>G (p.Leu3344Val) variant has been reported in the published literature in an individual with a personal and/or family history of cancer (PMID: 31853058 (2020)). The frequency of this variant in the general population, 0.000004 (1/251056 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Fulgent Genetics, |
RCV005008159 | SCV005633999 | uncertain significance | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Familial prostate cancer | 2024-05-21 | criteria provided, single submitter | clinical testing |