ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5506G>A (p.Gly1836Arg) (rs766739164)

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
Invitae RCV001087232 SCV000282781 likely benign Familial adenomatous polyposis 1 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000478919 SCV000569766 uncertain significance not provided 2018-10-11 criteria provided, single submitter clinical testing This variant is denoted APC c.5506G>A at the cDNA level, p.Gly1836Arg (G1836R) at the protein level, and results in the change of a Glycine to an Arginine (GGA>AGA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC Gly1836Arg was observed at an allele frequency of 0.13% (45/34,386) in individuals of Latino ancestry in large population cohorts (Lek 2016). This variant is located in the 20-amino acid repeat beta-catenin down-regulating domain and the SAMP repeats/axin binding domain (Azzopardi 2008). In-silico analysis, which includes protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available evidence, it is unclear whether APC Gly1836Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000561275 SCV000667290 likely benign Hereditary cancer-predisposing syndrome 2018-06-20 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;Other data supporting benign classification
PreventionGenetics,PreventionGenetics RCV000478919 SCV000805435 uncertain significance not provided 2017-01-10 criteria provided, single submitter clinical testing
Color RCV000561275 SCV000902919 benign Hereditary cancer-predisposing syndrome 2017-02-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000478919 SCV001133349 benign not provided 2019-02-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001192984 SCV001361482 likely benign not specified 2019-10-10 criteria provided, single submitter clinical testing Variant summary: APC c.5506G>A (p.Gly1836Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 250906 control chromosomes, predominantly at a frequency of 0.0013 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 18 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 Latino origin. To our knowledge, no occurrence of c.5506G>A in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Five 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 (3x likely benign/benign, 2x VUS). 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.