ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4597A>G (p.Lys1533Glu)

dbSNP: rs1060502418
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000464981 SCV000549588 uncertain significance Hereditary breast ovarian cancer syndrome 2016-05-03 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 1533 of the BRCA2 protein (p.Lys1533Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. Experimental studies have shown that this missense change does not significantly alter the interaction between BRCA2 and RAD51 in cell culture (PMID: 21601571). In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985530 SCV001133804 uncertain significance not provided 2019-05-07 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV003157532 SCV003850642 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 RCV004802005 SCV005424443 uncertain significance BRCA2-related cancer predisposition 2024-02-22 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 1533 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function. This variant did not impact BRCA2-RAD51 interaction in a mammalian two-hybrid assay (PMID: 21601571). This variant has not been reported in individuals affected with BRCA2-related disorders in the literature, but has been reported in an unaffected individual (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_008244). 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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