ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6485A>G (p.Asn2162Ser) (rs1064795210)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480456 SCV000570803 uncertain significance not provided 2017-02-07 criteria provided, single submitter clinical testing This variant is denoted APC c.6485A>G at the cDNA level, p.Asn2162Ser (N2162S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Asn2162Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Asparagine and Serine share similar properties, this is considered a conservative amino acid substitution. APC Asn2162Ser occurs at a position that is conserved in mammals and is located in the basic domain (Azzopardi 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether APC Asn2162Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000534129 SCV000647645 uncertain significance Familial adenomatous polyposis 1 2018-04-12 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 2162 of the APC protein (p.Asn2162Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 421555). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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.