ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4991T>C (p.Ile1664Thr)

dbSNP: rs863224590
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000198889 SCV000254187 likely benign Hereditary breast ovarian cancer syndrome 2024-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571680 SCV000661213 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-12 criteria provided, single submitter clinical testing The p.I1664T variant (also known as c.4991T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 4991. The isoleucine at codon 1664 is replaced by threonine, an amino acid with 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.
Baylor Genetics RCV001334182 SCV001526955 uncertain significance Fanconi anemia complementation group D1 2018-02-05 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
University of Washington Department of Laboratory Medicine, University of Washington RCV000571680 SCV003852266 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 RCV003996988 SCV004828979 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 1664 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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.

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