ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8017A>G (p.Arg2673Gly) (rs767286063)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198905 SCV000254044 uncertain significance Familial adenomatous polyposis 1 2017-02-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 2673 of the APC protein (p.Arg2673Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs767286063, ExAC 0.02%) but has not been reported in the literature in individuals with a APC-related disease. ClinVar contains an entry for this variant (Variation ID: 216183). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000766698 SCV000570747 uncertain significance not provided 2018-10-26 criteria provided, single submitter clinical testing This variant is denoted APC c.8017A>G at the cDNA level, p.Arg2673Gly (R2673G) at the protein level, and results in the change of an Arginine to a Glycine (AGA>GGA). This variant was observed in at least one individual with breast cancer (Yehia 2018). APC Arg2673Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the EB1 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 Arg2673Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000572076 SCV000667366 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000572076 SCV000681903 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-11 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202229 SCV000257034 uncertain significance not specified no assertion criteria provided research

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