Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130146 | SCV000184980 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-01-24 | criteria provided, single submitter | clinical testing | The p.A3345T variant (also known as c.10033G>A and10261G>A), located in coding exon 26 of the BRCA2 gene, results from a G to A substitution at nucleotide position 10033. The alanine at codon 3345 is replaced by threonine, 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. This amino acid position is highly conserved on sequence alignment of 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.A3345T remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985456 | SCV001133663 | uncertain significance | not provided | 2019-01-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002514726 | SCV003251691 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 3345 of the BRCA2 protein (p.Ala3345Thr). This variant is not present in population databases (gnomAD no frequency). 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: 141567). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Baylor Genetics | RCV004567104 | SCV005059187 | uncertain significance | Familial cancer of breast | 2023-11-14 | criteria provided, single submitter | clinical testing |