ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6724A>G (p.Ser2242Gly) (rs201375478)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000034395 SCV000149023 uncertain significance not provided 2018-10-09 criteria provided, single submitter clinical testing This variant is denoted APC c.6724A>G at the cDNA level, p.Ser2242Gly (S2242G) at the protein level, and results in the change of a Serine to a Glycine (AGT>GGT). This variant was observed in at least one individual with colon cancer and in a patient with breast cancer (Tung 2015, Yurgelun 2015, Yurgelun 2017). APC Ser2242Gly was observed at an allele frequency of 0.025% (31/126386) in individuals of European ancestry in large population cohorts (Lek 2016). This variant is located in the basic 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 Ser2242Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115114 SCV000183843 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Invitae RCV000200083 SCV000254030 likely benign Familial adenomatous polyposis 1 2017-12-27 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000034395 SCV000333806 uncertain significance not provided 2015-09-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000211930 SCV000591200 uncertain significance not specified 2012-04-13 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000211930 SCV000600137 uncertain significance not specified 2016-09-22 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515374 SCV000611340 uncertain significance Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma 2017-05-23 criteria provided, single submitter clinical testing
Color RCV000115114 SCV000681821 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-13 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000664301 SCV000788230 likely benign Familial multiple polyposis syndrome 2018-04-01 criteria provided, single submitter research The APC variant designated as NM_000038.5:c.6724A>G (p.Ser2242Gly) is classified as likely benign. This variant was observed or imputed to be present in two individuals in the same family that are over seventy years old without colorectal cancer, one of whom was documented to not have polyps on colonoscopy. These observations are not consistent with either attenuated or classic familial adenomatous polyposis syndromes. This variant is in ExAC (rs201375478) and is present in approximately 1/3355 individuals of European ancestry, which is greater than the incidence of familial adenomatous polyposis (1/8,000 to 1/10,000). This genomic position is conserved. This variant was also found in co-occurrence with an MSH2 pathogenic mutation. Bayesian analysis integrating all of this data (Tavtigian et al, 2018, PMID:29300386) gives about 1% probability of pathogenicity, which is consistent with a classification of likely benign. A modest (less than 2 fold) increase in cancer risk due to this variant cannot be entirely excluded. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034395 SCV000043134 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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