Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000581934 | SCV000688810 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001363535 | SCV001559651 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1166 of the BRCA2 protein (p.Val1166Ala). This variant is present in population databases (rs762886975, gnomAD 0.0009%). This missense change has been observed in individual(s) with prostate cancer (PMID: 25111659). ClinVar contains an entry for this variant (Variation ID: 491244). 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. |
Institute for Clinical Genetics, |
RCV003237950 | SCV002010383 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
University of Washington Department of Laboratory Medicine, |
RCV000581934 | SCV003846651 | 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). |
All of Us Research Program, |
RCV004802268 | SCV004845172 | uncertain significance | BRCA2-related cancer predisposition | 2024-07-20 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with alanine at codon 1166 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 a family with a history of prostate cancer (PMID: 25111659). This variant has been identified in 1/250862 chromosomes 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. |
Ambry Genetics | RCV000581934 | SCV004915395 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-26 | criteria provided, single submitter | clinical testing | The c.3497T>C (p.V1166A) alteration is located in exon 11 (coding exon 10) of the BRCA2 gene. This alteration results from a T to C substitution at nucleotide position 3497, causing the valine (V) at amino acid position 1166 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |