Fetal anomalies
Gene: CDK8

CDK8 (cyclin dependent kinase 8)
EnsemblGeneIds (GRCh38): ENSG00000132964
EnsemblGeneIds (GRCh37): ENSG00000132964
OMIM: 603184, Gene2Phenotype
CDK8 is in 4 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.

Panel Version: 1.836

Comment on list classification: Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'Q4_21_rating' tag)
Created: 2 Nov 2021, noon | Last Modified: 2 Nov 2021, noon

Panel Version: 1.750

Created: 2 Nov 2021, noon
Last Modified: 2 Nov 2021, noon
Panel version: 1.836

Rhiannon Mellis (Great Ormond Street Hospital)

Green List (high evidence)

This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.

Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).

Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.

Already rated Green on the following other PanelApp panel(s): Intellectual disability; Severe paediatric disorders

Details of review:
Aggarwal et al 2020 report a heterozygous nonsense variant in a fetus with ventriculomegaly and Ebstein anomaly resulting in IUFD. Post-mortem found additionally congenital diaphragmatic hernia, common atrium and facial dysmorphism. This nonsense variant is at the same position as a hotspot for missense variants reported in a paediatric cohort (Calpena et al 2019, PMID: 30905399) with overlapping but milder phenotype: half of the 12 children in that cohort had cardiac defects, most had dysmorphic features - hence Aggarwal et al propose that this is a more severe (prenatal) presentation of the same multiple malformation syndrome, caused here by a nonsense rather than missense mutation.
Sources: Literature, Expert Review
Created: 29 Oct 2021, 1:48 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Syndromic developmental disorder with hypotonia and behavioural abnormalities

Publications

PMID: 31742715
30905399

Created: 29 Oct 2021, 1:48 p.m.

Panel version: 1.749

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green

Phenotypes

Intellectual developmental disorder with hypotonia and behavioral abnormalities, OMIM:618748

OMIM

603184

Clinvar variants

Variants in CDK8

Penetrance

None

Publications

Panels with this gene