ClinVar Miner

Submissions for variant NM_000038.5(APC):c.8389A>G (p.Ser2797Gly) (rs147287751)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129949 SCV000184772 likely benign Hereditary cancer-predisposing syndrome 2017-10-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),No disease association in appropriately sized case-control study(ies),Other data supporting benign classification
Color RCV000129949 SCV000902847 likely benign Hereditary cancer-predisposing syndrome 2016-11-22 criteria provided, single submitter clinical testing
Counsyl RCV000198030 SCV000488295 uncertain significance Familial adenomatous polyposis 1 2016-02-19 criteria provided, single submitter clinical testing
Fulgent Genetics RCV000515282 SCV000611342 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
GeneDx RCV000656753 SCV000292468 uncertain significance not provided 2018-03-13 criteria provided, single submitter clinical testing This variant is denoted APC c.8389A>G at the cDNA level, p.Ser2797Gly (S2797G) at the protein level, and results in the change of a Serine to a Glycine (AGC>GGC). This variant has been reported in individuals with breast cancer (Tung 2015, Dominguez-Valentin 2017) APC Ser2797Gly was observed at an allele frequency of 0.015% (18/122,528) in individuals of European ancestry in large population cohorts (Lek 2016). APC Ser2797Gly is located in the hDLG 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 Ser2797Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000283075 SCV000452057 uncertain significance APC-Associated Polyposis Disorders 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000198030 SCV000254049 uncertain significance Familial adenomatous polyposis 1 2018-07-01 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 2797 of the APC protein (p.Ser2797Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. This variant is present in population databases (rs147287751, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals affected with breast and colorectal cancer (PMID: 25186627, 28608266, 28135145). ClinVar contains an entry for this variant (Variation ID: 141436). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000198030 SCV000838162 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
PreventionGenetics RCV000656753 SCV000805481 uncertain significance not provided 2017-06-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235404 SCV000600167 uncertain significance not specified 2017-07-17 criteria provided, single submitter clinical testing

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