Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589775 | SCV000695044 | uncertain significance | not provided | 2016-03-08 | criteria provided, single submitter | clinical testing | Variant summary: c.7142C>A affects a non-conserved nucleotide, resulting in amino acid change from Pro to Gln. 4/5 in-silico tools predict this variant to be damaging. This variant was found in 1/121362 control chromosomes at a frequency of 0.0000082, which does not exceed the maximal expected frequency of a pathogenic allele (0.0007503). The variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical laboratories nor was it evaluated for functional impact by in vivo/vitro studies. Due to the absence of clinical information and lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available. |
| Labcorp Genetics |
RCV001853973 | SCV002148487 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-11-16 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 2381 of the BRCA2 protein (p.Pro2381Gln). This variant is present in population databases (rs746751519, gnomAD 0.003%). 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: 495495). 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. |
| Ambry Genetics | RCV002367988 | SCV002662307 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-28 | criteria provided, single submitter | clinical testing | The p.P2381Q variant (also known as c.7142C>A), located in coding exon 13 of the BRCA2 gene, results from a C to A substitution at nucleotide position 7142. The proline at codon 2381 is replaced by glutamine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003471934 | SCV004211861 | uncertain significance | Familial cancer of breast | 2023-10-16 | criteria provided, single submitter | clinical testing |