ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7556A>G (p.Asp2519Gly)

dbSNP: rs1766510088
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003771154 SCV001564705 uncertain significance Familial adenomatous polyposis 1 2024-12-12 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2519 of the APC protein (p.Asp2519Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1059095). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002395833 SCV002672857 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-08 criteria provided, single submitter clinical testing The p.D2519G variant (also known as c.7556A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7556. The aspartic acid at codon 2519 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly 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.
All of Us Research Program, National Institutes of Health RCV004803671 SCV005424971 uncertain significance Classic or attenuated familial adenomatous polyposis 2024-04-25 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 2519 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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