Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001534619 | SCV001751538 | likely pathogenic | Intellectual developmental disorder with autism and macrocephaly | 2021-07-15 | criteria provided, single submitter | case-control | The variant c.3725G>A (p.(Arg1242Gln)) in exon 19 of the CHD8-gene is not found in the gnomAD database and it affects a highly conserved nucleotide a highly conserved amino acid within a protein domain and there is a small physicochemical difference between Arg and Gln. This variant has a pathogenic computational verdict based on 12 pathogenic predictions from BayesDel_addAF, DANN, DEOGEN2, EIGEN, FATHMM-MKL, LIST-S2, M-CAP, MVP, MutationAssessor, MutationTaster, PolyPhen-2 and SIFT vs 1 benign prediction from PrimateAI. This variant was previously detected as a de novo variant in individuals with an autism / intellectual disability disorder (PMID: 27824329; 25363760; 28191890; 28714951; 31981491) and it was found in an affected individual in our clinic. Thus, we classify this variant as a likely pathogenic mutation. ACMG criteria used for classification: PS4, PM2, PP3, PP4, PP5. |