Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: CD40LGComment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.Created: 14 Oct 2020, 12:34 p.m. | Last Modified: 14 Oct 2020, 12:34 p.m.
Panel Version: 2.236
The following PubMed IDs were added to gene CD40LG (OMIM gene MIM#300386): 27189378;19931163;25840720;27697500. These publications have been associated with the gene by the immunodeficiencies subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208
Publications
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
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
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): CD40LG (TNFSF5) .PanelApp HGNC gene symbol check: CD40LG . IUIS Disease: CD40 ligand deficiency (CD154) . IUIS Inheritance: XL .T cells: N/A, .B cells: sIgM+, IgD+ cells present, absent sIgG+, IgA+ and IgE+ cells, .IUIS Other affected cells: N/A. IUIS Associated features: Neutropenia, thrombocytopenia, hemolytic anemia, opportunistic infections, biliary tract and liver disease, Cryptosporidium infections. IUIS Major category: Immunodeficiencies affecting cellular and humoral immunity. IUIS Subcategory: Combined Immunodeficiencies Generally Less Profound than Severe Combined ImmunodeficiencyCreated: 2 Jul 2018, 10:35 a.m.
Comment on list classification: changed from Amber to Green rating, there is enough evidence in the literature to support the PID phenotypeCreated: 4 May 2018, 2:29 p.m.
This is most common form of HIGM syndrome and results from a defect or deficiency of a protein that is found on the surface of activated T-lymphocytes. The affected protein is called CD40 ligand because it binds, or ligates, to a protein on B-lymphocytes called CD40. CD40 ligand is made by a gene on the X-chromosome. Therefore, this primary immunodeficiency disease is inherited as an X-linked recessive trait.Created: 4 May 2018, 2:28 p.m.
Comment on publications: Added publications to support C40L variants causing a PID phenotype- more than three unrelated affecteds (over 30) and animal models. Added GenerviewCreated: 4 May 2018, 2 p.m.
Comment on phenotypes: added phenotypes and synonyms from OMIM and orphanetCreated: 4 May 2018, 12:56 p.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: 20 Apr 2018, 12:25 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: CD40L (CD154), PanelApp HGNC gene symbol check: CD40LG, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Class switch recombination defects (CSR) / HIGM syndromes / CSR defects and Hyper IgM (HIGM) syndromesCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CD40LG, GRID_Gene_Symbol: CD40LG, GRID_Transcript_ENS_Community submitted: ENST00000370629, GRID_Transcript_RefSeq: NM_000074.2, GRID_Transcript_ENS_used_on_Production: ENST00000370629Created: 17 Apr 2018, 12:12 p.m.
Gene: cd40lg has been classified as Green List (High Evidence).
Source Other was added to CD40LG. Publications for gene CD40LG were updated from 7679801; 7678782; 7679206; 8094231; 7586644; 17146684; 7882172; 11875495; 20301576 to 11875495; 7678782; 7679801; 27189378; 8094231; 20301576; 27697500; 19931163; 17146684; 7882172; 25840720; 7586644; 7679206 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to CD40LG.
Source North West GLH was added to CD40LG.
Source London North GLH was added to CD40LG.
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 CD40LG were set to Immunodeficiency, X-linked, with hyper-IgM, CD40 ligand deficiency, CSR defects and Hyper IgM (HIGM) syndromes, Hyper-IGM immunodeficiency, X-linked, XHIM, Hyper-IGM syndrome, HIGM, IHIS, Immunodeficiency 3, IMD3, Hyper-IgM syndrome due to CD40 ligand deficiency, Hyper-IgM syndrome due to CD40L deficiency, Hyper-IgM syndrome type 1, HIGM1, Neutropenia, thrombocytopenia, hemolytic anemia, opportunistic infections, biliary tract and liver disease, Cryptosporidium infections, Immunodeficiencies affecting cellular and humoral immunity
IUIS Classification February 2018 was added to CD40LG. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to CD40LG. Panel: Primary immunodeficiency disorders
Gene: cd40lg has been classified as Green List (High Evidence).
Publications for CD40LG were set to 7679801; 7678782; 7679206; 8094231; 7586644; 17146684; 7882172; 11875495; 20301576
This gene has been classified as Green List (High Evidence).
Publications for CD40LG were set to 7679801; 7678782; 7679206; 8094231; 7586644; 17146684; 7882172; 11875495
Phenotypes for CD40LG were set to Immunodeficiency, X-linked, with hyper-IgM; CD40 ligand deficiency; CSR defects and Hyper IgM (HIGM) syndromes; Hyper-IGM immunodeficiency, X-linked; XHIM; Hyper-IGM syndrome; HIGM; IHIS; Immunodeficiency 3; IMD3; Hyper-IgM syndrome due to CD40 ligand deficiency; Hyper-IgM syndrome due to CD40L deficiency; Hyper-IgM syndrome type 1; HIGM1
Phenotypes for CD40LG were set to Immunodeficiency, X-linked, with hyper-IgM; CD40 ligand deficiency; CSR defects and Hyper IgM (HIGM) syndromes; Hyper-IGM immunodeficiency, X-linked; XHIM; Hyper-IGM syndrome; Hyper-IGM syndrome; HIGM; IHIS; Immunodeficiency 3; IMD3
Expert Review Amber was added to CD40LG. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to CD40LG. Panel: Primary immunodeficiency disorders Phenotypes for gene CD40LG were set to Immunodeficiency, X-linked, with hyper-IgM, CD40 ligand deficiency, CSR defects and Hyper IgM (HIGM) syndromes
Phenotypes for gene CD40LG were set to Immunodeficiency, X-linked, with hyper-IgM, CD40 ligand deficiency
GRID V2.0 was added to CD40LG. Panel: Primary immunodeficiency disorders Phenotypes for gene CD40LG were set to Immunodeficiency, X-linked, with hyper-IgM, CD40 ligand deficiency
CD40LG Source: GOSH PID 20171141 was removed from gene: CD40LG
GOSH PID v.8.0 was added to CD40LG. Panel: Primary immunodeficiency disorders
CD40LG was added to Primary immunodeficiency disorders panel. Sources: GOSH PID 20171141
CD40LG was created by Louise Daugherty