ClinVar Miner

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

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130791 SCV000185685 likely benign Hereditary cancer-predisposing syndrome 2018-08-29 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Invitae RCV000199213 SCV000254001 likely benign Familial adenomatous polyposis 1 2020-11-26 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.
St. Jude 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 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130791 SCV000911205 benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000482678 SCV000916506 likely benign not specified 2021-03-01 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 9.6e-05 in 250976 control chromosomes, predominantly at a frequency of 0.0014 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 20 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 or African-American origin. c.2476T>G has been reported in the literature in individuals affected with breast cancer and pediatric cancer (Tung_2014, Zhang_2015). These reports 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. Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=1), likely benign (n=3) and benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.