ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2567A>G (p.Tyr856Cys)

dbSNP: rs864622122
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204510 SCV000259393 uncertain significance Hereditary breast ovarian cancer syndrome 2022-04-04 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 219500). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 856 of the BRCA1 protein (p.Tyr856Cys). 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 BRCA1 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001328453 SCV001519594 uncertain significance not specified 2021-03-07 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2567A>G (p.Tyr856Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251004 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2567A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. At-least one co-occurrence withan other pathogenic variant has been observed at our laboratory (BRCA2 c.6592C>T, p.R2318*), providing supporting evidence for a benign role. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157446 SCV003847572 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).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001355649 SCV001550592 uncertain significance not provided no assertion criteria provided clinical testing

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