ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6236A>C (p.Asp2079Ala)

gnomAD frequency: 0.00003  dbSNP: rs779413228
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000579432 SCV000681789 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-18 criteria provided, single submitter clinical testing
Invitae RCV003537232 SCV000832846 uncertain significance Familial adenomatous polyposis 1 2023-10-16 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 2079 of the APC protein (p.Asp2079Ala). This variant is present in population databases (rs779413228, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 489476). 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. 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 RCV000579432 SCV001187144 likely benign Hereditary cancer-predisposing syndrome 2023-07-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800796 SCV002046221 uncertain significance not provided 2020-09-16 criteria provided, single submitter clinical testing
GeneDx RCV001800796 SCV002526524 uncertain significance not provided 2022-06-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual undergoing multi-gene cancer panel testing due to a personal history of a Lynch syndrome-related cancer and/or polyps (Yurgelun 2015); This variant is associated with the following publications: (PMID: 25980754)

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