ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.2288A>G (p.Asp763Gly)

gnomAD frequency: 0.00019  dbSNP: rs201483304
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478070 SCV000569102 uncertain significance not provided 2017-02-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CNTNAP2 gene. The D763G variant has not beenpublished as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D763G variantwas not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBIExome Sequencing Project and was not observed with any significant frequency in the 1000 Genomes Project. TheD763G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure asthese residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position whereamino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis is inconsistent inits predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currentlyavailable information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001039323 SCV001202850 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 glycine, which is neutral and non-polar, at codon 763 of the CNTNAP2 protein (p.Asp763Gly). This variant is present in population databases (rs201483304, gnomAD 0.05%). 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: 420314). 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 RCV002446928 SCV002734744 uncertain significance Inborn genetic diseases 2017-12-14 criteria provided, single submitter clinical testing The p.D763G variant (also known as c.2288A>G), located in coding exon 15 of the CNTNAP2 gene, results from an A to G substitution at nucleotide position 2288. The aspartic acid at codon 763 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well 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.

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