Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165239 | SCV000215953 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-02 | criteria provided, single submitter | clinical testing | The p.P1133S variant (also known as c.3397C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 3397. The proline at codon 1133 is replaced by serine, an amino acid with similar properties. 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. Based on the available evidence, the clinical significance of this variant remains unclear. |
Labcorp Genetics |
RCV000227293 | SCV000283209 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | 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: 185755). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1133 of the BRCA2 protein (p.Pro1133Ser). |
Gene |
RCV001762376 | SCV002008691 | uncertain significance | not provided | 2023-09-06 | criteria provided, single submitter | clinical testing | Identified in individuals with breast, renal, and other cancers (Peker Eyuboglu et al., 2020; Duzkale et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 3625C>T; This variant is associated with the following publications: (PMID: 32377563, 31851867, 29884841, Duzkale2020[Article]) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001762376 | SCV002046319 | uncertain significance | not provided | 2024-08-13 | criteria provided, single submitter | clinical testing | The BRCA2 c.3397C>T (p.Pro1133Ser) variant has been reported in the published literature in an individual with a personal or family history of breast cancer (PMID: 31851867 (2020)), and described to be located in a region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV003137693 | SCV003806815 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2022-09-23 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 moderated, BP4 supporting |
University of Washington Department of Laboratory Medicine, |
RCV000165239 | SCV003851920 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |