Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: WAS
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
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): WAS .PanelApp HGNC gene symbol check: WAS . IUIS Disease: Wiskott-Aldrich syndrome . IUIS Inheritance: XL , .B cells: Normal numbers, .IUIS Other affected cells: N/A. IUIS Associated features: Thrombocytopenia with small platelets, recurrent bacterial and viral infections, bloody diarrhea, eczema, lymphoma, autoimmune disease, IgA nephropathy, vasculitis. XL thrombocytopenia is a mild form of WAS, and XL neutropenia is caused by missense mutations in the GTPase binding domain of WASp. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Immunodeficiency with Congenital Thrombocytopenia. // OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): WAS .PanelApp HGNC gene symbol check: WAS . IUIS Disease: X-linked neutropenia/ myelodysplasia . IUIS Inheritance: XL , .B cells: N/A, .IUIS Other affected cells: N. IUIS Associated features: Neutropenia, myeloid maturation arrest, monocytopenia, variable lymphoid anomalies . IUIS Major category: Congenital defects of phagocyte number or function. IUIS Subcategory: Congenital NeutropeniasCreated: 2 Jul 2018, 11:02 a.m.
Comment on mode of pathogenicity: Gain of function variants cause X-linked neutropenia/ myelodysplasia WASCreated: 13 Jun 2018, 2:58 p.m.
from Congenital neutropaenia panel
Sophie Hambleton (Newcastle University)
[email protected]
Green List (high evidence)
Gain of function variants of WAS cause neutropenia (disruption of autoinhibition). LOF variants cause the allelic disorders X-linked thrombocytopenia and Wiskott Aldrich Syndrome
19 Oct 2015, 11:23 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
severe congenital neutropenia; myelodysplasia
Publications
11242115
16804117
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the commentsCreated: 18 Apr 2018, 3:56 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: WASP (x-linked), PanelApp HGNC gene symbol check: WAS, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / Wiskott-Aldrich syndrome (WAS) / Wiskott-Aldrich syndrome (WAS); Other well defined PIDs / Wiskott-Aldrich syndrome (WAS) / X-linked thrombocytopenia with mutations in WASP; Phagocytic disorders / Congenital neutropenia / Congenital neutropeniaCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: WAS, GRID_Gene_Symbol: WAS, GRID_Transcript_ENS_Community submitted: ENST00000376701, GRID_Transcript_RefSeq: NM_000377.2, GRID_Transcript_ENS_used_on_Production: ENST00000376701Created: 17 Apr 2018, 12:12 p.m.
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Added the tag ‘gene-therapy-trial’ as this gene is within the Gene Therapy Panel available here: https://panelapp.genomicsengland.co.uk/panels/412Created: 14 May 2018, 10:02 a.m.
Comment on list classification: Gene added by a reviewer, with a second green rating. Multiple cases of patients with Wiskott-Aldrich syndrome in OMIM.Created: 3 Jun 2016, 3:19 p.m.
Comment when marking as ready: Associated with phenotype in OMIM, not in G2P. Three expert reviews recommend Green. Found in 1/4 sources. Three variants reported in the literature in three unrelated families with Neutropenia, severe congenital, X-linked, 300299Created: 25 May 2016, 8:55 a.m.
Source NHS GMS was added to WAS.
Source North West GLH was added to WAS.
Source London North GLH was added to WAS.
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.
Phenotypes for gene: WAS were set to Wiskott-Aldrich syndrome; Neutropenia, severe congenital, X-linked, 300299; X-linked thrombocytopenia; Wiskott-Aldrich syndrome (WAS); X-linked thrombocytopenia with mutations in WASP; Congenital neutropenia; Thrombocytopenia with small platelets, recurrent bacterial and viral infections, bloody diarrhea, eczema, lymphoma, autoimmune disease, IgA nephropathy, vasculitis; XL thrombocytopenia is a mild form of WAS, and XL neutropenia is caused by missense mutations in the GTPase binding domain of WASp; Combined immunodeficiencies with associated or syndromic features; Neutropenia, myeloid maturation arrest, monocytopenia, variable lymphoid anomalies; Congenital defects of phagocyte number or function
IUIS Classification February 2018 was added to WAS. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to WAS. Panel: Primary immunodeficiency disorders
Gene: was has been classified as Green List (High Evidence).
Mode of pathogenicity for gene: WAS was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
ESID Registry 20171117 was added to WAS. Panel: Primary immunodeficiency disorders Phenotypes for gene WAS were set to Wiskott-Aldrich syndrome, Neutropenia, severe congenital, X-linked, 300299, X-linked thrombocytopenia, Wiskott-Aldrich syndrome (WAS), X-linked thrombocytopenia with mutations in WASP, Congenital neutropenia
Phenotypes for gene WAS were set to Wiskott-Aldrich syndrome, Neutropenia, severe congenital, X-linked, 300299, X-linked thrombocytopenia
GRID V2.0 was added to WAS. Panel: Primary immunodeficiency disorders Phenotypes for gene WAS were set to Wiskott-Aldrich syndrome, Neutropenia, severe congenital, X-linked, 300299, X-linked thrombocytopenia
WAS Source: GOSH PID 20171207 was removed from gene: WAS
GOSH PID v.8.0 was added to WAS. Panel: Primary immunodeficiency disorders
Phenotypes for WAS were set to Wiskott-Aldrich syndrome; Neutropenia, severe congenital, X-linked, 300299; X-linked thrombocytopenia
GOSH PID 20171207 was added to WAS. Panel: Primary immunodeficiency disorders
Phenotypes for WAS were set to Neutropenia, severe congenital, X-linked, 300299; Wiskott Aldrich Syndrome; x-linked thrombocytopenia
Congenital neutropaenia v1.22 was added to WAS. Panel: Primary immunodeficiency disorders Publications for gene WAS was set to ['11242115', '16804117']
WAS was added to Primary immunodeficiency disorders panel. Sources: Expert Review Green, Combined B and T cell defect v1.12
WAS was created by Louise Daugherty