ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8266A>G (p.Ile2756Val) (rs146115809)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122809 SCV000166066 likely benign Familial adenomatous polyposis 1 2020-11-19 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148374 SCV000190068 uncertain significance Colorectal adenoma 2014-06-01 criteria provided, single submitter research Low GERP score may suggest that this variant belongs in a lower pathogenicity class
GeneDx RCV000587542 SCV000209559 uncertain significance not provided 2018-06-11 criteria provided, single submitter clinical testing This variant is denoted APC c.8266A>G at the cDNA level, p.Ile2756Val (I2756V) at the protein level, and results in the change of an Isoleucine to a Valine (ATA>GTA). This variant was observed in an individual with multiple colorectal adenomas (Azzopardi 2008). APC Ile2756Val was observed at an allele frequency of 0.05% (11/24,030) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is located in the EB1 binding domain (Azzopardi 2008). 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 Ile2756Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000122809 SCV000487910 uncertain significance Familial adenomatous polyposis 1 2015-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000493019 SCV000581417 likely benign Hereditary cancer-predisposing syndrome 2019-04-24 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587542 SCV000694141 likely benign not provided 2017-05-26 criteria provided, single submitter clinical testing Variant summary: The APC c.8266A>G (p.Ile2756Val) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant. This variant was found in 10/123264 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.000866 (9/10396). This frequency is about 12 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. This variant has been reported in one colorectal adenomas patient without strong evidence for causality. In addition, multiple clinical diagnostic laboratories classified this variant as uncertain significance, without evidence for independent evaluation. Taken together, the this variant is classified as likely benign.
Color Health, Inc RCV000493019 SCV000911089 likely benign Hereditary cancer-predisposing syndrome 2016-05-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587542 SCV001133376 likely benign not provided 2018-08-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001157355 SCV001318917 likely benign APC-Associated Polyposis Disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Baylor Genetics RCV000122809 SCV001481389 uncertain significance Familial adenomatous polyposis 1 2020-02-23 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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