Submissions for variant NM_014141.6(CNTNAP2):c.2609T>C (p.Val870Ala)

gnomAD frequency: 0.00096  dbSNP: rs138481453

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124367	SCV000167798	benign	not specified	2013-06-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago	RCV000124367	SCV000247060	likely benign	not specified	2016-12-23	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000124367	SCV000612857	likely benign	not specified	2019-03-29	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727344	SCV000707731	uncertain significance	not provided	2017-05-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086897	SCV000766448	likely benign	Cortical dysplasia-focal epilepsy syndrome	2024-01-25	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001291659	SCV001480238	uncertain significance	See cases	2019-09-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426676	SCV002744524	uncertain significance	Inborn genetic diseases	2017-09-30	criteria provided, single submitter	clinical testing	The p.V870A variant (also known as c.2609T>C), located in coding exon 17 of the CNTNAP2 gene, results from a T to C substitution at nucleotide position 2609. The valine at codon 870 is replaced by alanine, 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.
Revvity Omics, Revvity	RCV001086897	SCV003831089	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2021-07-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000124367	SCV005204673	likely benign	not specified	2024-06-18	criteria provided, single submitter	clinical testing	Variant summary: CNTNAP2 c.2609T>C (p.Val870Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00021 in 251474 control chromosomes, predominantly at a frequency of 0.0028 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in CNTNAP2 causing Autism, Susceptibility To, 15 phenotype. To our knowledge, no occurrence of c.2609T>C in individuals affected with Autism, Susceptibility To, 15 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 136819). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004748593	SCV005347502	uncertain significance	CNTNAP2-related disorder	2024-04-03	no assertion criteria provided	clinical testing	The CNTNAP2 c.2609T>C variant is predicted to result in the amino acid substitution p.Val870Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.29% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.