Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165059 | SCV000215760 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-07-10 | criteria provided, single submitter | clinical testing | The p.A2351V variant (also known as c.7052C>T and 7280C>T), located in coding exon 13 of the BRCA2 gene, results from a C to T substitution at nucleotide position 7052. The alanine at codon 2351 is replaced by valine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs80358932. This variant was not reported in population-based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 42,000 alleles tested) in our clinical cohort (includes this individual). Based on protein sequence alignment, this amino acid position is not well conserved in available vertebrate species, and valine is the reference amino acid in several 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.A2351V remains unclear. |
| Labcorp Genetics |
RCV000793502 | SCV000932856 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-04-03 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2351 of the BRCA2 protein (p.Ala2351Val). This variant is not present in population databases (gnomAD no frequency). 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: 126128). This missense change has been observed in individual(s) with BRCA2-related conditions (PMID: 10923033). |
| Baylor Genetics | RCV004566989 | SCV005059073 | uncertain significance | Familial cancer of breast | 2024-02-06 | criteria provided, single submitter | clinical testing | |
| Breast Cancer Information Core |
RCV000113698 | SCV000147010 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2003-12-23 | no assertion criteria provided | clinical testing |