ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1054T>C (p.Tyr352His) (rs542343726)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167496 SCV000218354 benign Hereditary cancer-predisposing syndrome 2019-03-14 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification;Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
Invitae RCV000470929 SCV000560437 likely benign Hereditary breast and ovarian cancer syndrome 2020-02-04 criteria provided, single submitter clinical testing
GeneDx RCV000485522 SCV000569857 likely benign not specified 2017-07-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Health, Inc RCV000167496 SCV000903401 likely benign Hereditary cancer-predisposing syndrome 2018-05-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000485522 SCV001426859 uncertain significance not specified 2020-07-17 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1054T>C (p.Tyr352His) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 247576 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1054T>C has been reported in the literature in at least one individual affected with breast cancer (Lara_2012). This report however, does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer Syndrome. The authors of this study report that this variant may not be the main cause of the disease as this variant generates biochemically similar changes in amino acids. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. One of the ClinVar submitters states without providing specific evidence for independent evaluation, that the variant was seen in trans with a mutation or in homozygous state in individual without severe disease for that gene (SCV000218354.3). Based on the evidence outlined above, the variant was classified as VUS-possibly benign until additional evidence of clinical or functional importance becomes available.

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