ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4648G>C (p.Glu1550Gln)

dbSNP: rs80358695
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Michigan Medical Genetics Laboratories, University of Michigan RCV000210981 SCV000267768 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2016-04-21 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine, Queen's University RCV000496491 SCV000588094 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022836 SCV001184617 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-05 criteria provided, single submitter clinical testing The p.E1550Q variant (also known as c.4648G>C), located in coding exon 10 of the BRCA2 gene, results from a G to C substitution at nucleotide position 4648. The glutamic acid at codon 1550 is replaced by glutamine, 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.
Invitae RCV001321133 SCV001511951 uncertain significance Hereditary breast ovarian cancer syndrome 2021-10-28 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 21520333). This variant is present in population databases (rs80358695, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1550 of the BRCA2 protein (p.Glu1550Gln). ClinVar contains an entry for this variant (Variation ID: 225743). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV001022836 SCV003850684 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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