ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2451G>T (p.Lys817Asn) (rs767686668)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569494 SCV000665425 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Integrated Genetics/Laboratory Corporation of America RCV000781098 SCV000918923 uncertain significance not specified 2018-04-16 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.2451G>T (p.Lys817Asn) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was observed with an allele frequency of 8.4e-06 in 239036 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (8.4e-06 vs 0.00075), allowing no conclusion about variant significance. The variant, c.2451G>T, has been reported in a colorectal cancer cell line (Ikediobi 2006, Mouradov 2014). These reports however, do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "uncertain significance." Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758875 SCV000887776 uncertain significance not provided 2018-06-14 criteria provided, single submitter clinical testing

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