ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5566C>T (p.His1856Tyr)

gnomAD frequency: 0.00003  dbSNP: rs755791142
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001043657 SCV001207413 uncertain significance Hereditary breast ovarian cancer syndrome 2023-01-31 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1856 of the BRCA2 protein (p.His1856Tyr). This variant is present in population databases (rs755791142, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 841439). 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.
Genetic Services Laboratory, University of Chicago RCV001819757 SCV002067801 uncertain significance not specified 2019-11-18 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV003158324 SCV003848917 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).
Ambry Genetics RCV003158324 SCV004005526 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-04 criteria provided, single submitter clinical testing The p.H1856Y variant (also known as c.5566C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 5566. The histidine at codon 1856 is replaced by tyrosine, an amino acid with 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.
All of Us Research Program, National Institutes of Health RCV004004763 SCV004846597 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-11-09 criteria provided, single submitter clinical testing

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