ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7166G>A (p.Ser2389Asn) (rs779287035)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000526527 SCV000647696 uncertain significance Familial adenomatous polyposis 1 2018-07-16 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 2389 of the APC protein (p.Ser2389Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an APC-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000564175 SCV000667356 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Integrated Genetics/Laboratory Corporation of America RCV000586700 SCV000694109 uncertain significance not provided 2017-07-03 criteria provided, single submitter clinical testing Variant summary: The c.7166G>A (p.Ser2389Asn) in APC gene is a missense variant involves a mildly conserved nucleotide and 3/5 in silico tools predict deleterious outcome. The variant is located within the basic domain, however no functional studies supporting deleterious outcome of this alteration on the protein function have been published at the time of evaluation. The variant is absent from the control population dataset of ExAC, but is present at a low frequency in gnomAD (0.000004081; 1/245052 chrs tested), which does not exceed the maximal expected allele frequency for a disease causing allele in APC gene (0.00007). To our knowledge, the variant has not been reported in affected individuals via published reports nor has it been cited by reputable databases/clinical laboratories. Taken together, the variant was classified as VUS, until new information becomes available.
Fulgent Genetics,Fulgent Genetics RCV000765790 SCV000897179 uncertain significance Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000564175 SCV000905274 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-26 criteria provided, single submitter clinical testing

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