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Intellectual disability

Gene: CHD3

Green List (high evidence)

CHD3 (chromodomain helicase DNA binding protein 3)
EnsemblGeneIds (GRCh38): ENSG00000170004
EnsemblGeneIds (GRCh37): ENSG00000170004
OMIM: 602120, Gene2Phenotype
CHD3 is in 4 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team: appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene to Green.
Created: 25 Feb 2019, 4:16 p.m.
Comment on publications: added publication to support gene-disease association
Created: 25 Feb 2019, 4:02 p.m.
Comment on phenotypes: added MIMid from OMIM
Created: 25 Feb 2019, 3:58 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID 30397230 is a collaborative study reporting on the phenotype of 35 individuals including 4 subjects from the DDD study, (most) with de novo mutations in CHD3.

Common features include developmental delay, variable degrees of intellectual disability, impaired speech and language (all 3 were universal features) as well as macrocephaly (in approximately 60%) or vision problems. Widely spaced eyes and high/broad/prominent forehead were among the most constant facial features (noted in around 80% each).

The majority of the variants reported are missense and cluster within the helicase domain although exceptions of missense variants in other domains or loss-of-function variants are provided. A few variants were recurrent and/or concerned the same residue.

Two pairs of affected siblings are reported, in one case this was explained by maternal mosaicism for the mutation.

Perturbed ATPase and/or chromatin remodeling activity relative to wild-type were demonstrated although both gain and loss of these activities were noted depending on the variant tested.

CHD3 is intolerant to both loss-of-function and missense variants (pLI of 1.0 and Z-score of +7.15).

As a result this gene can be considered for inclusion in the ID panel as green.
Sources: Expert Review, Literature
Created: 11 Nov 2018, 12:58 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay; Intellectual disability; Macrocephaly

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • Global developmental delay
  • Intellectual disability
  • Macrocephaly
  • Snijders Blok-Campeau syndrome, 618205
OMIM
602120
Clinvar variants
Variants in CHD3
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

25 Feb 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: chd3 has been classified as Green List (High Evidence).

25 Feb 2019, Gel status: 0

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: CHD3 were set to 30397230

25 Feb 2019, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: CHD3 were changed from Global developmental delay; Intellectual disability; Macrocephaly to Global developmental delay; Intellectual disability; Macrocephaly; Snijders Blok-Campeau syndrome, 618205

11 Nov 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: CHD3 was added gene: CHD3 was added to Intellectual disability. Sources: Expert Review,Literature Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CHD3 were set to 30397230 Phenotypes for gene: CHD3 were set to Global developmental delay; Intellectual disability; Macrocephaly Penetrance for gene: CHD3 were set to unknown Review for gene: CHD3 was set to GREEN