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Primary immunodeficiency

Gene: STAT1

Green List (high evidence)

STAT1 (signal transducer and activator of transcription 1)
EnsemblGeneIds (GRCh38): ENSG00000115415
EnsemblGeneIds (GRCh37): ENSG00000115415
OMIM: 600555, Gene2Phenotype
STAT1 is in 10 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)

Monoallelic gain-of-function causes a combined immunodeficiency with prominent chronic mucocutaneous candidiasis and autoimmunity.
Monoallelic hypomorphic mutation causes susceptibility to mycobacterial disease (MSMD).
Biallelic loss of function causes susceptibility to both mycobacterial and viral disease.

Evidence for each of these 3 aetiologies is strong.
Created: 11 Jun 2018, 12:21 p.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Mode of pathogenicity
Other

Eleanor Williams (Genomics England Curator)

Comment on list classification: STAT1 is associated with Immunodeficiency 31A,B, and C in OMIM.
More than 3 unrelated cases reported for each disorder. Both gain and loss of function variants reported (gain - Liu et al. (2011) (PMID: 21727188), Soltesz et al. (2013) (PMID: 23709754), Sampaio et al. (2013) (PMID: 23541320) , Uzel et al. (2013) (PMID: 23534974), Carey et al (2018) (PMID: 29702748) and loss - Mork et al 2015 (PMID: 26513235).
Created: 1 May 2018, 4:15 p.m.
Comment on mode of pathogenicity: Both gain of function and loss of function variants reported. See rating review.
Created: 1 May 2018, 4:15 p.m.
Comment on publications: Added relevant publications.
Created: 1 May 2018, 4:14 p.m.
Comment on phenotypes: Added MIM IDs
Created: 1 May 2018, 3:09 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): STAT1 .PanelApp HGNC gene symbol check: STAT1 . IUIS Disease: STAT1 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: T and NK cells and monocytes. IUIS Associated features: Severe viral infections, mycobacterial infection. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Predisposition to Severe Viral Infection. // OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): STAT1 .PanelApp HGNC gene symbol check: STAT1 . IUIS Disease: STAT1 . IUIS Inheritance: AD GOF .T cells: Normal , .B cells: N/A, .IUIS Other affected cells: T cells, B cells, monocytes. IUIS Associated features: CMC, various fungal, bacterial and viral (HSV) infections, auto-immunity (thyroiditis, diabetes, cytopenias), enteropathy. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Predisposition to Mucocutaneous Candidiasis. // OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): STAT1 .PanelApp HGNC gene symbol check: STAT1 . IUIS Disease: STAT1 deficiency . IUIS Inheritance: AD .T cells: Variable, .B cells: N/A, .IUIS Other affected cells: M + L. IUIS Associated features: Susceptibility to mycobacteria, Salmonella, . IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Mendelian Susceptibility to mycobacterial disease (MSMD)
Created: 2 Jul 2018, 11 a.m.
Comment on mode of pathogenicity: from Expert review comment: Monoallelic gain-of-function causes a combined immunodeficiency with prominent chronic mucocutaneous candidiasis and autoimmunity. Monoallelic hypomorphic mutation causes susceptibility to mycobacterial disease (MSMD). Biallelic loss of function causes susceptibility to both mycobacterial and viral disease. Evidence for each of these 3 aetiologies is strong.
Created: 13 Jun 2018, 10:37 a.m.
Comment on mode of inheritance: updated MOI from external expert review
Created: 13 Jun 2018, 10:37 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, 2:24 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: STAT1, PanelApp HGNC gene symbol check: STAT1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Combined immunodeficiencies / Combined immunodeficiency (CID) / Combined immunodeficiency; Defects in innate immunity / Chronic mucocutaneous candidiasis (CMC) / Chronic mucocutaneous candidiasis (CMC); Phagocytic disorders / Defects with susceptibility to mycobacterial infection (MSMD) / Defects with susceptibility to mycobacterial infection (MSMD)
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: STAT1, GRID_Gene_Symbol: STAT1, GRID_Transcript_ENS_Community submitted: ENST00000361099, GRID_Transcript_RefSeq: NM_007315.3, GRID_Transcript_ENS_used_on_Production: ENST00000361099
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • ESID Registry 20171117
  • GRID V2.0
  • GOSH PID v.8.0
Phenotypes
  • Immunodeficiency 31A, mycobacteriosis, autosomal dominant 614892
  • Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive 613796
  • Immunodeficiency 31C, autosomal dominant 614162
  • Immunodeficiency 31A, mycobacteriosis
  • Candidiasis, familial, 7
  • Combined immunodeficiency
  • Chronic mucocutaneous candidiasis (CMC)
  • Defects with susceptibility to mycobacterial infection (MSMD)
  • Severe viral infections, mycobacterial infection
  • CMC, various fungal, bacterial and viral (HSV) infections, auto-immunity (thyroiditis, diabetes, cytopenias), enteropathy
  • Susceptibility to mycobacteria, Salmonella
  • Defects in Intrinsic and Innate Immunity
OMIM
600555
Clinvar variants
Variants in STAT1
Penetrance
None
Publications
Mode of Pathogenicity
Other - please provide details in the comments
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 STAT1.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to STAT1.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to STAT1.

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.

1 Jul 2018, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: STAT1 were set to Immunodeficiency 31A, mycobacteriosis, autosomal dominant 614892; Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive 613796; Immunodeficiency 31C, autosomal dominant 614162; Immunodeficiency 31A, mycobacteriosis; Candidiasis, familial, 7; Combined immunodeficiency; Chronic mucocutaneous candidiasis (CMC); Defects with susceptibility to mycobacterial infection (MSMD); Severe viral infections, mycobacterial infection; CMC, various fungal, bacterial and viral (HSV) infections, auto-immunity (thyroiditis, diabetes, cytopenias), enteropathy; Susceptibility to mycobacteria, Salmonella; 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 STAT1. 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 STAT1. Panel: Primary immunodeficiency disorders

13 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: stat1 has been classified as Green List (High Evidence).

13 Jun 2018, Gel status: 3

Set mode of pathogenicity

Louise Daugherty (Genomics England Curator)

Mode of pathogenicity for gene: STAT1 was changed to Other - please provide details in the comments

13 Jun 2018, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: STAT1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

1 May 2018, Gel status: 3

Gene classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

1 May 2018, Gel status: 2

Set mode of pathogenicity

Eleanor Williams (Genomics England Curator)

Mode of pathogenicity for STAT1 was changed to Other - please provide details in the comments

1 May 2018, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for STAT1 were set to 21727188; 23709754; 23541320; 23534974; 26513235; 11452125; 12590259; 29702748

1 May 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for STAT1 were set to Immunodeficiency 31A, mycobacteriosis, autosomal dominant 614892; Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive 613796; Immunodeficiency 31C, autosomal dominant 614162; Immunodeficiency 31A, mycobacteriosis; Candidiasis, familial, 7; Combined immunodeficiency; Chronic mucocutaneous candidiasis (CMC); Defects with susceptibility to mycobacterial infection (MSMD)

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).

19 Apr 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for STAT1 were set to Immunodeficiency 31A, mycobacteriosis, autosomal dominant; Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive; Immunodeficiency 31C, autosomal dominant; Immunodeficiency 31A, mycobacteriosis; Candidiasis, familial, 7; Combined immunodeficiency; Chronic mucocutaneous candidiasis (CMC); Defects with susceptibility to mycobacterial infection (MSMD)

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to STAT1. Panel: Primary immunodeficiency disorders Phenotypes for gene STAT1 were set to Immunodeficiency 31A, mycobacteriosis, autosomal dominant, Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, Immunodeficiency 31C, autosomal dominant, Immunodeficiency 31A, mycobacteriosis, Candidiasis, familial, 7, Candidiasis, familial, 7, Combined immunodeficiency, Chronic mucocutaneous candidiasis (CMC), Defects with susceptibility to mycobacterial infection (MSMD)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene STAT1 were set to Immunodeficiency 31A, mycobacteriosis, autosomal dominant, Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, Immunodeficiency 31C, autosomal dominant, Immunodeficiency 31A, mycobacteriosis, Candidiasis, familial, 7, Candidiasis, familial, 7

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

GRID V2.0 was added to STAT1. Panel: Primary immunodeficiency disorders Phenotypes for gene STAT1 were set to Immunodeficiency 31A, mycobacteriosis, autosomal dominant, Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, Immunodeficiency 31C, autosomal dominant, Immunodeficiency 31A, mycobacteriosis, Candidiasis, familial, 7

6 Apr 2018, Gel status: 1

Clear Sources

Louise Daugherty (Genomics England Curator)

STAT1 Source: GOSH PID 20171194 was removed from gene: STAT1

6 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

GOSH PID v.8.0 was added to STAT1. Panel: Primary immunodeficiency disorders

29 Mar 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

STAT1 was added to Primary immunodeficiency disorders panel. Sources: GOSH PID 20171194

29 Mar 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

STAT1 was created by Louise Daugherty