ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2225A>G (p.Gln742Arg)

gnomAD frequency: 0.00001  dbSNP: rs1282599125
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001316100 SCV001506703 uncertain significance Hereditary breast ovarian cancer syndrome 2023-10-16 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 742 of the BRCA2 protein (p.Gln742Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 34326862). ClinVar contains an entry for this variant (Variation ID: 1017013). 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. 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.
Ambry Genetics RCV002431898 SCV002729709 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-15 criteria provided, single submitter clinical testing The p.Q742R variant (also known as c.2225A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 2225. The glutamine at codon 742 is replaced by arginine, 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002431898 SCV003846590 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).
Color Diagnostics, LLC DBA Color Health RCV002431898 SCV004361252 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-09 criteria provided, single submitter clinical testing This missense variant replaces glutamine with arginine at codon 742 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.
All of Us Research Program, National Institutes of Health RCV004005083 SCV004824379 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces glutamine with arginine at codon 742 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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