Submissions for variant NM_014141.6(CNTNAP2):c.3193C>A (p.Leu1065Ile)

dbSNP: rs146225600

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000116781	SCV000150762	uncertain significance	not provided	2014-01-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000116781	SCV000240737	likely benign	not provided	2021-03-09	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000116781	SCV000334951	uncertain significance	not provided	2015-09-08	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000187159	SCV000612860	uncertain significance	not specified	2017-04-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312080	SCV000847178	likely benign	Inborn genetic diseases	2024-06-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079431	SCV001001875	likely benign	Cortical dysplasia-focal epilepsy syndrome	2025-01-27	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000116781	SCV001715977	uncertain significance	not provided	2019-07-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000187159	SCV005887637	likely benign	not specified	2025-01-22	criteria provided, single submitter	clinical testing	Variant summary: CNTNAP2 c.3193C>A (p.Leu1065Ile) results in a 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 0.00024 in 1,607,240 control chromosomes, predominantly at a frequency of 0.0048 within the African or African-American subpopulation in the gnomAD database (v4.1 dataset), including 1 homozygote. 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.3193C>A 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: 128804). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003975014	SCV004792095	likely benign	CNTNAP2-related disorder	2023-05-06	no assertion criteria provided	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).