Submissions for variant NM_001170629.2(CHD8):c.3454G>A (p.Val1152Ile)

dbSNP: rs1888123647

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001270822	SCV001451586	uncertain significance	Autism spectrum disorder	2019-04-26	criteria provided, single submitter	clinical testing	The CHD8 c.3454G>A (p.Val1152Ile) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database in a region of good sequence coverage, so the variant is presumed to be rare. The Val1152Ile residue is predicted to be highly evolutionarily conserved based on several in silico tools. Based on the limited evidence, the p.Val1152Ile variant is classified as a variant of uncertain significance for autism spectrum disorder.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479306	SCV004223364	uncertain significance	not specified	2023-11-01	criteria provided, single submitter	clinical testing	Variant summary: CHD8 c.3454G>A (p.Val1152Ile) results in a conservative amino acid change located in the Helicase, C-terminal domain (IPR001650) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248802 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3454G>A in individuals affected with CHD8-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.