ClinVar Miner

Submissions for variant NM_000038.6(APC):c.848G>A (p.Arg283Gln) (rs149154604)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131302 SCV000186274 likely benign Hereditary cancer-predisposing syndrome 2019-03-13 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
GeneDx RCV000211895 SCV000209485 uncertain significance not provided 2018-04-25 criteria provided, single submitter clinical testing This variant is denoted APC c.848G>A at the cDNA level, p.Arg283Gln (R283Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has been reported in at least one individual with a Lynch syndrome-associated tumor and/or colon polyps (Yurgelun 2015). APC Arg283Gln was observed at an allele frequency of 0.16% (16/10,140) in individuals of Ashkenazi Jewish ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Arg283Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000167872 SCV000218518 likely benign Familial adenomatous polyposis 1 2020-12-07 criteria provided, single submitter clinical testing
Counsyl RCV000167872 SCV000489595 uncertain significance Familial adenomatous polyposis 1 2016-10-26 criteria provided, single submitter clinical testing
Mendelics RCV000167872 SCV000838070 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131302 SCV000910684 likely benign Hereditary cancer-predisposing syndrome 2016-03-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779725 SCV000916486 likely benign not specified 2020-09-14 criteria provided, single submitter clinical testing Variant summary: APC c.848G>A (p.Arg283Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.4e-05 in 251064 control chromosomes. The observed variant frequency is approximately 1.2 fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), suggesting that the variant is benign. c.848G>A has been reported in the literature in individuals affected with Lynch Syndrome (Yurgelun_2015). This report does not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign n=3, VUS n=3). 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.