ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3194T>C (p.Ile1065Thr)

gnomAD frequency: 0.00001  dbSNP: rs431825303
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132329 SCV000187417 likely benign Hereditary cancer-predisposing syndrome 2023-11-08 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000168025 SCV000218677 uncertain significance Hereditary breast ovarian cancer syndrome 2024-10-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1065 of the BRCA2 protein (p.Ile1065Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 27978560). ClinVar contains an entry for this variant (Variation ID: 96787). 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.
Counsyl RCV000082908 SCV000785752 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2017-11-20 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000132329 SCV000906061 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284559 SCV001470408 uncertain significance not provided 2019-12-17 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000132329 SCV003851757 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 RCV004804081 SCV004845121 uncertain significance BRCA2-related cancer predisposition 2024-08-13 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 1065 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 not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has been reported in an individual affected with rectal cancer (PMID: 27978560). 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.
Sharing Clinical Reports Project (SCRP) RCV000082908 SCV000114982 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2012-05-01 no assertion criteria provided clinical testing
BRCAlab, Lund University RCV000082908 SCV004243601 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2020-03-02 no assertion criteria provided clinical testing

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