ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2584A>G (p.Asn862Asp)

gnomAD frequency: 0.00001  dbSNP: rs755221428
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003651866 SCV000552614 uncertain significance Familial adenomatous polyposis 1 2023-09-27 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. This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 862 of the APC protein (p.Asn862Asp). This variant is present in population databases (rs755221428, gnomAD 0.002%). 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: 411453). 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.
Ambry Genetics RCV000572675 SCV000675932 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-04 criteria provided, single submitter clinical testing The p.N862D variant (also known as c.2584A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 2584. The asparagine at codon 862 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000572675 SCV001342402 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-29 criteria provided, single submitter clinical testing This missense variant replaces asparagine with aspartic acid at codon 862 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 hereditary cancer in the literature. This variant has been identified in 2/251106 chromosomes 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.