ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5994A>C (p.Gln1998His)

dbSNP: rs554663691
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001221658 SCV001393717 uncertain significance Hereditary breast ovarian cancer syndrome 2019-07-02 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1998 of the BRCA2 protein (p.Gln1998His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA2-related conditions.
Ambry Genetics RCV002356943 SCV002657132 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-17 criteria provided, single submitter clinical testing The p.Q1998H variant (also known as c.5994A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 5994. The glutamine at codon 1998 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002356943 SCV003850844 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).

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