Submissions for variant NM_014141.6(CNTNAP2):c.3112G>A (p.Asp1038Asn)

gnomAD frequency: 0.00006  dbSNP: rs144003410

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187158	SCV000240736	uncertain significance	not provided	2022-08-13	criteria provided, single submitter	clinical testing	Reported previously in a control individual and was not predicted to be deleterious; however, zygosity of the variant or the phenotype of the individual was not provided (Bakkaloglu et al., 2008); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18179895)
Invitae	RCV000532742	SCV000645100	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2023-11-01	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 1038 of the CNTNAP2 protein (p.Asp1038Asn). This variant is present in population databases (rs144003410, gnomAD 0.07%). 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: 205220). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Illumina Laboratory Services, Illumina	RCV000532742	SCV001322227	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Athena Diagnostics Inc	RCV000187158	SCV002770956	uncertain significance	not provided	2022-01-26	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002485267	SCV002778736	uncertain significance	Autism, susceptibility to, 15; Cortical dysplasia-focal epilepsy syndrome	2021-10-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002517855	SCV003689373	uncertain significance	Inborn genetic diseases	2021-10-04	criteria provided, single submitter	clinical testing	The c.3112G>A (p.D1038N) alteration is located in exon 19 (coding exon 19) of the CNTNAP2 gene. This alteration results from a G to A substitution at nucleotide position 3112, causing the aspartic acid (D) at amino acid position 1038 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.