ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.3427G>A (p.Asp1143Asn)

gnomAD frequency: 0.00009  dbSNP: rs765950760
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000502340 SCV000594172 uncertain significance not specified 2016-02-17 criteria provided, single submitter clinical testing
GeneDx RCV000767188 SCV000621997 uncertain significance not provided 2017-11-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CNTNAP2 gene. The D1143N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D1143N variant is observed in 5/34420 (0.001%) alleles from individuals of Latino background (Lek et al., 2016). The D1143N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Baylor Genetics RCV001336150 SCV001529464 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2018-07-20 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001336150 SCV002277992 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1143 of the CNTNAP2 protein (p.Asp1143Asn). This variant is present in population databases (rs765950760, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 434799). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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 RCV002455967 SCV002614494 uncertain significance Inborn genetic diseases 2019-09-21 criteria provided, single submitter clinical testing The p.D1143N variant (also known as c.3427G>A), located in coding exon 21 of the CNTNAP2 gene, results from a G to A substitution at nucleotide position 3427. The aspartic acid at codon 1143 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly 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.

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.