ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7967A>G (p.Asp2656Gly)

dbSNP: rs1463203731
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587099 SCV000694129 uncertain significance not provided 2017-02-09 criteria provided, single submitter clinical testing Variant summary: The APC c.7967A>G (p.Asp2656Gly) variant involves the alteration of a conserved nucleotide, which 4/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a damaging outcome, although these predictions have yet to be functionally assessed. The variant of interest has not been observed in large, broad control populations (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)."
Labcorp Genetics (formerly Invitae), Labcorp RCV002530881 SCV000768149 uncertain significance Familial adenomatous polyposis 1 2024-07-22 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 2656 of the APC protein (p.Asp2656Gly). 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: 495374). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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.
Color Diagnostics, LLC DBA Color Health RCV001185311 SCV001351498 uncertain significance Hereditary cancer-predisposing syndrome 2025-03-17 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 2656 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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.
Ambry Genetics RCV001185311 SCV002677184 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-07 criteria provided, single submitter clinical testing The p.D2656G variant (also known as c.7967A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7967. The aspartic acid at codon 2656 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.
Baylor Genetics RCV002530881 SCV004205906 uncertain significance Familial adenomatous polyposis 1 2023-05-19 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004002391 SCV004835744 uncertain significance Classic or attenuated familial adenomatous polyposis 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 2656 of the APC protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer 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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