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Primary immunodeficiency

Gene: TYK2

Green List (high evidence)

TYK2 (tyrosine kinase 2)
EnsemblGeneIds (GRCh38): ENSG00000105397
EnsemblGeneIds (GRCh37): ENSG00000105397
OMIM: 176941, Gene2Phenotype
TYK2 is in 5 panels

5 reviews

Kimberly Gilmour (Great Ormond Street Hopsital)

Green List (high evidence)

agree with green gene
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

YES- this is covered on our targeted exome
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Eleanor Williams (Genomics England Curator)

Comment on phenotypes: Added MIM number to Immunodeficiency 35
Created: 21 Jun 2018, 3:33 p.m.
Comment on publications: Added publications relating to reported cases with relevant variants.
Created: 21 Jun 2018, 3:33 p.m.
Comment on list classification: More than 3 unrelated cases of plausible disease causing mutations in the TYK2 gene in patients with Immunodeficiency 35.
Created: 21 Jun 2018, 3:31 p.m.
In OMIM TYK2 is associated with Immunodeficiency 35. Evidence comes from 3 publications. Minegishi et al. (2006)(PMID: 17088085) report a 22-year-old Japanese male with immunodeficiency-35 and a homozygous deletion of GCTT at nucleotide 550 in the TYK2 gene, resulting in a frameshift and premature termination of the protein at amino acid 90. Immunoblot analysis detected no TYK2 protein in the patient's T cells. Both of the patient's parents, who were healthy, were heterozygous for the TYK2 mutation. Kilic et al. (2012)(PMID: 22402565) report a Turkish male, born of consanguineous parents, with IMD35 and a homozygous truncating mutation (9-bp deletion resulting in a frameshift and premature termination at codon 767) in the TYK2 gene , resulting in complete loss of function. Kilic et al. (2012) suggested that lack of TYK2 resulted in defective IL12 signaling and impaired production of gamma-interferon. Kreins et al. (2015)(PMID: 26304966) report 6 patients from 4 unrelated families with IMD35, with 4 different homozygous truncating mutations in the TYK2 gene. The mutations segregated with the disorder in the families.
Created: 21 Jun 2018, 3:30 p.m.

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TYK2 .PanelApp HGNC gene symbol check: TYK2 . IUIS Disease: Tyk2 deficiency . IUIS Inheritance: AR , .B cells: N/A, .IUIS Other affected cells: Normal, but multiple cytokine signaling defect. IUIS Associated features: Susceptibility to intracellular bacteria (mycobacteria, Salmonella), viruses, +/- elevated IgE. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Mendelian Susceptibility to mycobacterial disease (MSMD)
Created: 2 Jul 2018, 10:35 a.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s)
GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.
Created: 19 Apr 2018, 11:04 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: Tyk2, PanelApp HGNC gene symbol check: TYK2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / Hyper IgE syndromes / Hyper IgE syndrome (HIES)
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TYK2, GRID_Gene_Symbol: TYK2, GRID_Transcript_ENS_Community submitted: ENST00000525621, GRID_Transcript_RefSeq: NM_003331.4, GRID_Transcript_ENS_used_on_Production: ENST00000525621
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • Expert Review Green
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • Immunodeficiency 35 611521
  • Hyper IgE syndrome (HIES)
  • Susceptibility to intracellular bacteria (mycobacteria, Salmonella), viruses, +/- elevated IgE
  • Defects in Intrinsic and Innate Immunity
OMIM
176941
Clinvar variants
Variants in TYK2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TYK2.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to TYK2.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to TYK2.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.

6 Jul 2018, Gel status: 4

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: tyk2 has been classified as Green List (High Evidence).

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TYK2 were set to Immunodeficiency 35 611521, Hyper IgE syndrome (HIES), Susceptibility to intracellular bacteria (mycobacteria, Salmonella), viruses, +/- elevated IgE, Defects in Intrinsic and Innate Immunity

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to TYK2. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to TYK2. Panel: Primary immunodeficiency disorders

21 Jun 2018, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TYK2 were set to Immunodeficiency 35 611521; Hyper IgE syndrome (HIES)

21 Jun 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TYK2 were set to 17088085; 22402565; 26304966

21 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tyk2 has been classified as Green List (High Evidence).

19 Apr 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to TYK2. Panel: Primary immunodeficiency disorders Phenotypes for gene TYK2 were set to Immunodeficiency 35, Hyper IgE syndrome (HIES)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TYK2 were set to Immunodeficiency 35

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

TYK2 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

TYK2 was created by Louise Daugherty