1. Panels
  2. Intellectual disability
  3. DOCK8
Genes in panel
Prev Next
Regions in panel
Prev Next

Intellectual disability

Gene: DOCK8

Amber List (moderate evidence)
DOCK8 (dedicator of cytokinesis 8)
EnsemblGeneIds (GRCh38): ENSG00000107099
EnsemblGeneIds (GRCh37): ENSG00000107099
OMIM: 611432, Gene2Phenotype
DOCK8 is in 12 panels

7 reviews

Dmitrijs Rots (Children's Clinical University Hospital)

Red List (low evidence)

DOCK8 is located in a region prone to CNVs (so hyper IgE is commonly caused by (biallelic) CNVs in this gene), BUT monoallelic CNVs (both deletions and duplication) in this gene are extremely common in general population:
https://gnomad.broadinstitute.org/gene/ENSG00000107099?dataset=gnomad_sv_r2_1
pLI of this gene is 0. Same is true for the KANK1 gene.
Reports associating DOCK8 CNVs with NDDs typically lack control groups (including all 4 papers referenced by Sarah Leigh), so they likely identified CNVs present in population.
Created: 24 Oct 2023, 2:10 p.m. | Last Modified: 24 Oct 2023, 2:10 p.m.
Panel Version: 5.315

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 24 Oct 2023, 2:10 p.m.
Last Modified: 24 Oct 2023, 2:10 p.m.
Panel version: 5.315

Arina Puzriakova (Genomics England Curator)

I don't know

The rating of this gene has been updated to Amber and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Created: 30 Jan 2023, 5:50 p.m. | Last Modified: 30 Jan 2023, 5:50 p.m.
Panel Version: 4.53
Created: 30 Jan 2023, 5:50 p.m.
Last Modified: 30 Jan 2023, 5:50 p.m.
Panel version: 4.53

Sarah Leigh (Genomics England Curator)

I don't know

Comment on phenotypes: Biallelic DOCK8 variants are associated with Hyper-IgE recurrent infection syndrome, autosomal recessive, OMIM:243700;combined immunodeficiency due to DOCK8 deficiency, MONDO:0009478
Created: 13 Sep 2022, 4:53 p.m. | Last Modified: 13 Sep 2022, 4:53 p.m.
Panel Version: 3.1711
Heterozygous rearrangements encompassing all or part of DOCK8 have been reported in cases with a range of neurodevelopmental features (PMIDs: 18060736; 29729439; 29930340; 33455084). The deletions (n=3), duplications (n=11) and interchromosomal translocations (n=7) may also include other genes, most commonly KANK1. Due to the involvement of other genes, inconsistancy of rearrangement type and phenotypic variability, an amber rating has been recommended for DOCK8 on the Intellectual disability panel (clinical indication R29).
Created: 13 Sep 2022, 4:49 p.m. | Last Modified: 13 Sep 2022, 4:49 p.m.
Panel Version: 3.1710

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

Phenotypes
Intellectual developmental disorder, autosomal dominant 2, OMIM:614113

Created: 13 Sep 2022, 4:49 p.m.
Last Modified: 13 Sep 2022, 4:49 p.m.
Panel version: 3.1710

Tracy Lester (Genetics laboratory, Oxford UK)

Red List (low evidence)

There is no evidence that I could find supporting biallelic variants in this gene being associated with ID/dev delay. DDD has no biallelic cases with pathogenic variants reported, and no evidence was found in the literature. There are some reports of microdels involving DOCK8 in cases with ID, but these are het and have been reported as being inherited in several cases (1764478). Zhang et al could find no evidence supporting a link to AD ID looking at carriers in their cases with AR immune disorders (19776401). Therefore, I think this gene should be rated red for the R29 panel.
Created: 26 Aug 2022, 3:01 p.m. | Last Modified: 26 Aug 2022, 3:01 p.m.
Panel Version: 3.1696

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

Created: 26 Aug 2022, 3:01 p.m.
Last Modified: 26 Aug 2022, 3:01 p.m.
Panel version: 3.1696

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HYPERIMMUNOGLOBULIN E RECURRENT INFECTION SYNDROME AUTOSOMAL RECESSIVE (AR-HIES)

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 5:34 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; gilissen_2014_known; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:19 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 2 Aug 2017, 4:57 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:31 a.m.

Panel version: 0.306

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • NHS GMS
  • Expert Review Amber
  • Victorian Clinical Genetics Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Intellectual developmental disorder, autosomal dominant 2, OMIM:614113
OMIM
611432
Clinvar variants
Variants in DOCK8
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

30 Jan 2023, Gel status: 2

Removed Tag, Removed Tag, Removed Tag, Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_22_rating was removed from gene: DOCK8. Tag Q3_22_MOI was removed from gene: DOCK8. Tag Q3_22_NHS_review was removed from gene: DOCK8. Tag Q3_22_expert_review was removed from gene: DOCK8.

30 Jan 2023, Gel status: 2

Added New Source, Added New Source, Set mode of inheritance, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Amber was added to DOCK8. Source NHS GMS was added to DOCK8. Mode of inheritance for gene DOCK8 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Rating Changed from Green List (high evidence) to Amber List (moderate evidence)

11 Oct 2022, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q3_22_MOI tag was added to gene: DOCK8.

11 Oct 2022, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q3_22_MOI was removed from gene: DOCK8.

13 Sep 2022, Gel status: 3

Added Tag, Added Tag, Added Tag, Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_22_rating tag was added to gene: DOCK8. Tag Q3_22_MOI tag was added to gene: DOCK8. Tag Q3_22_NHS_review tag was added to gene: DOCK8. Tag Q3_22_expert_review tag was added to gene: DOCK8.

13 Sep 2022, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: DOCK8 were changed from Mental retardation, autosomal dominant 2, 614113Hyper-IgE recurrent infection syndrome, autosomal recessive, 243700; HYPERIMMUNOGLOBULIN E RECURRENT INFECTION SYNDROME AUTOSOMAL RECESSIVE (AR-HIES) to Intellectual developmental disorder, autosomal dominant 2, OMIM:614113

13 Sep 2022, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: DOCK8 were set to

28 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to DOCK8.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

DOCK8 was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene DOCK8 was set to BIALLELIC, autosomal or pseudoautosomal

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

DOCK8 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen