ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2204C>T (p.Ala735Val) (rs147655929)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131447 SCV000186431 benign Hereditary cancer-predisposing syndrome 2015-06-19 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
GeneDx RCV000254627 SCV000209463 likely benign not specified 2017-08-29 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.
Invitae RCV000198399 SCV000252907 benign Familial adenomatous polyposis 1 2020-11-25 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000210149 SCV000266139 uncertain significance Colorectal cancer, susceptibility to 2015-11-20 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131447 SCV000681506 likely benign Hereditary cancer-predisposing syndrome 2016-06-24 criteria provided, single submitter clinical testing
Mendelics RCV000198399 SCV000838088 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000254627 SCV000918441 benign not specified 2020-11-27 criteria provided, single submitter clinical testing Variant summary: APC c.2204C>T (p.Ala735Val) results in a non-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 5.6e-05 in 249992 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in APC causing Familial Adenomatous Polyposis (5.6e-05 vs 7.1e-05), allowing no conclusion about variant significance. c.2204C>T has been reported in the literature in individuals affected with colorectal cancer (Yurgelun_2015, Yurgelun_2017), breast cancer (Tung_2014, Tung_2016), clinical laboratory APC sequencing cohort (Kerr_2013), patients undergoing multigene panel testing (Shirts_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. At-least two co-occurrences with other pathogenic variant(s) have been reported (APC c.994C>T, p.Arg332X, Kerr_2013; BRCA2 c.5351dupA, p.Asn1784Lysfs*3, Tung_2014), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight 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 with a majority consensus leaning towards benign(n=3)/likely benign(n=2). Based on the evidence outlined above, the variant was re-classified as benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000034406 SCV001500349 likely benign not provided 2021-01-01 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034406 SCV000043113 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
CSER _CC_NCGL, University of Washington RCV000417343 SCV000503559 likely benign Familial multiple polyposis syndrome 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 58 year old with 5-10 colon polyps and a family history of colon cancer.
3DMed Clinical Laboratory Inc RCV000677783 SCV000803939 uncertain significance Neoplasm of the liver 2017-01-09 no assertion criteria provided clinical testing

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