ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3497T>C (p.Val1166Ala)

dbSNP: rs762886975
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000581934 SCV000688810 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp 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, University Hospital TU Dresden, University Hospital TU Dresden RCV003237950 SCV002010383 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington 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, National Institutes of Health 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.

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