ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5993A>C (p.Gln1998Pro)

dbSNP: rs80358835
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164697 SCV000215365 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-28 criteria provided, single submitter clinical testing The p.Q1998P variant (also known as c.5993A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 5993. The glutamine at codon 1998 is replaced by proline, an amino acid with similar properties. This alteration has been reported with a carrier frequency of 0 in 7051 unselected breast cancer patients and 0.00018 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758916 SCV000887862 uncertain significance not provided 2018-05-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002515145 SCV003472654 uncertain significance Hereditary breast ovarian cancer syndrome 2022-07-05 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 185301). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1998 of the BRCA2 protein (p.Gln1998Pro).
University of Washington Department of Laboratory Medicine, University of Washington RCV000164697 SCV003850841 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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