ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7273A>G (p.Ser2425Gly) (rs730881261)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159572 SCV000209547 uncertain significance not provided 2014-08-06 criteria provided, single submitter clinical testing This variant is denoted APC c.7273A>G at the cDNA level, p.Ser2425Gly (S2425G) at the protein level, and results in the change of a Serine to a Glycine (AGT>GGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ser2425Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Serine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Ser2425Gly occurs at a position that is moderately conserved across species and is located in the Helicase ATP-binding domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether APC Ser2425Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000205013 SCV000261585 uncertain significance Familial adenomatous polyposis 1 2015-10-26 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 2425 of the APC protein (p.Ser2425Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. ClinVar contains an entry for this variant (Variation ID: 181820). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In addition, algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing through the creation of new splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare missense change with uncertain impact on protein function and mRNA splicing. It has been classified as a Variant of Uncertain Significance.

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