ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6173G>A (p.Gly2058Asp) (rs150140908)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000759438 SCV000209470 uncertain significance not provided 2017-02-16 criteria provided, single submitter clinical testing This variant is denoted APC c.6173G>A at the cDNA level, p.Gly2058Asp (G2058D) at the protein level, and results in the change of a Glycine to an Aspartic Acid (GGT>GAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Gly2058Asp was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Glycine and Aspartic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Gly2058Asp occurs at a position that is not conserved and is not located in a known functional domain (Azzopardi 2008). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether APC Gly2058Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000218693 SCV000276067 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Invitae RCV000524576 SCV000647630 uncertain significance Familial adenomatous polyposis 1 2018-12-12 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 2058 of the APC protein (p.Gly2058Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs150140908, ExAC 0.03%). This variant has been reported in individuals in the Universal Mutation Database (PMID: 24599579). ClinVar contains an entry for this variant (Variation ID: 181773). 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 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759438 SCV000888757 uncertain significance not provided 2018-08-10 criteria provided, single submitter clinical testing

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