ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5026A>G (p.Arg1676Gly) (rs370560998)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000120016 SCV000149009 likely benign not specified 2018-02-12 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.
CSER _CC_NCGL, University of Washington RCV000210376 SCV000190061 uncertain significance Familial multiple polyposis syndrome 2014-06-01 criteria provided, single submitter research Low GERP score may suggest that this variant belongs in a lower pathogenicity class
Ambry Genetics RCV000115100 SCV000213855 likely benign Hereditary cancer-predisposing syndrome 2018-06-26 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification;Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Invitae RCV000148369 SCV000254020 likely benign Familial adenomatous polyposis 1 2019-12-31 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000120016 SCV000257786 uncertain significance not specified 2015-06-19 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120016 SCV000591185 uncertain significance not specified 2016-08-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000120016 SCV000694067 likely benign not specified 2019-08-16 criteria provided, single submitter clinical testing Variant summary: APC c.5026A>G (p.Arg1676Gly) 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 0.00013 in 253514 control chromosomes (gnomAD). The observed variant frequency is approximately 2 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 benign. c.5026A>G has been reported in the literature in individuals affected with Familial Adenomatous Polyposis and colorectal cancer without strong evidence of causality (Zhang_2015 , Tung_2016; Kraus_2015). These reports do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. Ten other submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (5x likely benign and 5x uncertain significance). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics,PreventionGenetics RCV000587987 SCV000805419 uncertain significance not provided 2017-06-01 criteria provided, single submitter clinical testing
Mendelics RCV000148369 SCV000838128 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000735965 SCV000864154 uncertain significance Colorectal cancer 2016-06-01 criteria provided, single submitter research Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 51 year old male diagnosed with colon cancer at age 50. Family history of colorectal cancer and/or polyps. Patient also has the APC c.7399C>A variant. This interpretation considers GERP score and allele frequency data, in addition to published reports of the variant in the literature, available at the time of review.
Color RCV000115100 SCV000902642 likely benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
ITMI RCV000120016 SCV000084146 not provided not specified 2013-09-19 no assertion provided reference population
True Health Diagnostics RCV000115100 SCV000787837 likely benign Hereditary cancer-predisposing syndrome 2017-12-01 no assertion criteria provided clinical testing

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