Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165122 | SCV000215832 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-19 | criteria provided, single submitter | clinical testing | The p.P2477T variant (also known as c.7429C>A), located in coding exon 13 of the BRCA2 gene, results from a C to A substitution at nucleotide position 7429. The proline at codon 2477 is replaced by threonine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with breast cancer (Yao L et al. J Hum Genet, 2022 Nov;67:639-642). 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 this alteration remains unclear. |
| Labcorp Genetics |
RCV000531294 | SCV000635573 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2477 of the BRCA2 protein (p.Pro2477Thr). 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: 185664). 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. |
| Color Diagnostics, |
RCV000165122 | SCV000906555 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-30 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with threonine at codon 2477 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 35864222). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| All of Us Research Program, |
RCV004804741 | SCV004844405 | uncertain significance | BRCA2-related cancer predisposition | 2024-05-09 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV000656619 | SCV000778708 | uncertain significance | not provided | 2017-05-01 | no assertion criteria provided | clinical testing |