ClinVar Miner

Submissions for variant NM_001170629.2(CHD8):c.4846G>C (p.Asp1616His)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001263370 SCV001441412 uncertain significance Autistic disorder of childhood onset; Intellectual disability 2020-03-19 criteria provided, single submitter clinical testing The c.4846G>C (p.Asp1616His) variant detected in the CHD8 gene substitutes a well conserved Aspartic Acid for Histidine at amino acid 1616/2582 (coding exon 26/38).This variant is present with low frequency in gnomAD (1 heterozygote, 0 homozygotes; allele frequency: 3.19e-5) suggesting it is not a common benign variant in the populations represented in this database. In silico algorithms predict this variant to be Deleterious (Provean; score: -5.09) and Damaging (SIFT; score:0.005) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Asp1616 residue is not within a mapped domain of CHD8 (UniProkKB: Q9HCK8). Given the lack of compelling evidence for its pathogenicity, the c.4846G>C (p.Asp1616His) variant detected in the CHD8 gene is reported here as a Variant of Uncertain Significance.
GeneDx RCV001566846 SCV001790428 uncertain significance not provided 2020-08-26 no assertion criteria provided clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.