ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4897A>G (p.Ile1633Val)

dbSNP: rs80358713
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000044516 SCV000072529 uncertain significance Hereditary breast ovarian cancer syndrome 2024-07-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1633 of the BRCA2 protein (p.Ile1633Val). 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: 51736). 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.
Counsyl RCV000113355 SCV000488142 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2016-02-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV001023214 SCV001185059 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-21 criteria provided, single submitter clinical testing The p.I1633V variant (also known as c.4897A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4897. The isoleucine at codon 1633 is replaced by valine, an amino acid with highly similar properties. This amino acid position is poorly 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.
Color Diagnostics, LLC DBA Color Health RCV001023214 SCV001344941 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-05 criteria provided, single submitter clinical testing
GeneDx RCV002277134 SCV002567418 uncertain significance not provided 2022-08-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 5125A>G; This variant is associated with the following publications: (PMID: 24817641, 29884841, 31911673)
University of Washington Department of Laboratory Medicine, University of Washington RCV001023214 SCV003852183 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 RCV004803188 SCV005424459 uncertain significance BRCA2-related cancer predisposition 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 1633 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 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.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113355 SCV000146501 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 no assertion criteria provided clinical testing

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