Submissions for variant NM_014141.6(CNTNAP2):c.1220A>G (p.Asn407Ser)

gnomAD frequency: 0.00253  dbSNP: rs143877693

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081586	SCV000113517	benign	not specified	2013-10-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001529318	SCV000240725	likely benign	not provided	2022-05-13	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Genetic Services Laboratory, University of Chicago	RCV000081586	SCV000247052	likely benign	not specified	2016-07-05	criteria provided, single submitter	clinical testing
Invitae	RCV000527421	SCV000645074	benign	Cortical dysplasia-focal epilepsy syndrome	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316253	SCV000851270	uncertain significance	Inborn genetic diseases	2020-10-13	criteria provided, single submitter	clinical testing	The p.N407S variant (also known as c.1220A>G), located in coding exon 8 of the CNTNAP2 gene, results from an A to G substitution at nucleotide position 1220. The asparagine at codon 407 is replaced by serine, an amino acid with highly similar properties. This alteration has been detected in two individuals with autism spectrum disorder and two individuals with persistent developmental stuttering (Han TU et al. Neurobiol. Dis., 2014 Sep;69:23-31; Bakkaloglu B et al. Am. J. Hum. Genet., 2008 Jan;82:165-73). In addition, one functional study showed that this alteration maps to the L2 domain and is expected to have a mild effect on CNTNAP2 protein structure (Lu Z et al. J. Biol. Chem., 2016 Sep). This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on available evidence to date, the clinical significance of this alteration remains unclear.
Illumina Laboratory Services, Illumina	RCV000527421	SCV001320654	likely benign	Cortical dysplasia-focal epilepsy syndrome	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003915083	SCV004745353	likely benign	CNTNAP2-related condition	2019-10-14	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529318	SCV001742559	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529318	SCV001931002	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529318	SCV001973718	likely benign	not provided		no assertion criteria provided	clinical testing