ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2476T>G (p.Leu826Val) (rs145245264)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130791 SCV000185685 likely benign Hereditary cancer-predisposing syndrome 2017-07-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Subpopulation frequency in support of benign classification,In silico models in agreement (benign)
Invitae RCV000199213 SCV000254001 likely benign Familial adenomatous polyposis 1 2017-10-23 criteria provided, single submitter clinical testing
GeneDx RCV000482678 SCV000564566 likely benign not specified 2017-12-28 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 RCV000130791 SCV000911205 benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000482678 SCV000916506 likely benign not specified 2018-09-28 criteria provided, single submitter clinical testing Variant summary: APC c.2476T>G (p.Leu826Val) 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 0.00014 in 276878 control chromosomes, predominantly at a frequency of 0.0016 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 22.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. c.2476T>G has been reported in the literature in an individual affected with breast cancer and pediatric cancer. These report(s) do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761162 SCV000891078 uncertain significance B lymphoblastic leukemia lymphoma with t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1) 2017-03-07 no assertion criteria provided clinical testing

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