ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7414G>A (p.Ala2472Thr)

dbSNP: rs1580682363
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001026407 SCV001188782 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-17 criteria provided, single submitter clinical testing The p.A2472T variant (also known as c.7414G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 7414. The alanine at codon 2472 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV003537431 SCV002216300 uncertain significance Familial adenomatous polyposis 1 2021-07-23 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 827029). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 2472 of the APC protein (p.Ala2472Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine.
All of Us Research Program, National Institutes of Health RCV004004669 SCV004832077 uncertain significance Classic or attenuated familial adenomatous polyposis 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 2472 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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