ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3650A>C (p.Asn1217Thr) (rs138933660)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131570 SCV000186574 likely benign Hereditary cancer-predisposing syndrome 2018-02-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Internal frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance,In silico models in agreement (benign),Other data supporting benign classification
Invitae RCV000199645 SCV000254010 benign Familial adenomatous polyposis 1 2017-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000120014 SCV000292457 likely benign not specified 2017-09-25 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.
Counsyl RCV000199645 SCV000488023 uncertain significance Familial adenomatous polyposis 1 2015-12-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000120014 SCV000694035 likely benign not specified 2019-02-22 criteria provided, single submitter clinical testing Variant summary: The variant, APC c.3650A>C (p.Asn1217Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 277482 control chromosomes, predominantly at a frequency of 0.0023 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 32 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. The variant, c.3650A>C has been reported in the literature in an individual affected with cancer of cecum (Pearlman_2016). However, this report does 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 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and have classified the variant as likely benign/benign (X3) or uncertain significance (X2). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics,PreventionGenetics RCV000587732 SCV000805401 uncertain significance not provided 2018-01-10 criteria provided, single submitter clinical testing
Color RCV000131570 SCV000911206 benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
ITMI RCV000120014 SCV000084144 not provided not specified 2013-09-19 no assertion provided reference population

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