Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: C4A
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
Complete C4 deficiency is associated with susceptibility to infection and predisposes to SLECreated: 19 Jun 2018, 6:40 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
SLE predisposition; infections with encapsulated organisms
Publications
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): C4A+C4B .PanelApp HGNC gene symbol check: C4A . IUIS Disease: Complete C4 deficiency . IUIS Inheritance: AR .T cells: Normal , .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: SLE, infections with encapsulated organisms , partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/ACreated: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Changed Amber to Green from external review comment and further publications to support gene-disease associationCreated: 20 Jun 2018, 3:35 p.m.
Comment on phenotypes: Added phenotypes suggested from external expert review.Created: 20 Jun 2018, 3:34 p.m.
Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green.Created: 20 Jun 2018, 3:34 p.m.
Keep Amber for now, more suitable for autoinflammatory spectrum panel? Seek external clinical review.Created: 15 Jun 2018, 4:37 p.m.
Comment on publications: PMID:15294999 low C4A gene copy number is a risk factor for SLE susceptibilityCreated: 15 Jun 2018, 4:20 p.m.
Comment on phenotypes: Added MIMid from OMIM and phenotype from OrphanetCreated: 1 Jun 2018, 1:13 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: C4, PanelApp HGNC gene symbol check: C4A, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Complement component 4 deficiencyCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: C4A, GRID_Gene_Symbol: C4A, GRID_Transcript_ENS_Community submitted: ENST00000428956, GRID_Transcript_RefSeq: NM_007293.2, GRID_Transcript_ENS_used_on_Production: ENST00000428956Created: 17 Apr 2018, 12:12 p.m.
Source NHS GMS was added to C4A.
Source North West GLH was added to C4A.
Source London North GLH was added to C4A.
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 C4A were set to C4a deficiency, 614380, Complement component 4 deficiency, Immunodeficiency due to a classical component pathway complement deficiency, SLE predisposition, infections with encapsulated organisms, SLE, infections with encapsulated organisms , partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense, Complement Deficiencies
IUIS Classification February 2018 was added to C4A. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to C4A. Panel: Primary immunodeficiency disorders
Gene: c4a has been classified as Green List (High Evidence).
Gene: c4a has been classified as Green List (High Evidence).
Phenotypes for gene: C4A were set to C4a deficiency, 614380; Complement component 4 deficiency; Immunodeficiency due to a classical component pathway complement deficiency; SLE predisposition; infections with encapsulated organisms
Publications for gene: C4A were set to 15294999; 2295875; 22482068
Publications for gene: C4A were set to 15294999; 2295875
Publications for gene: C4A were set to 15294999
Phenotypes for gene: C4A were set to C4a deficiency, 614380; Complement component 4 deficiency; Immunodeficiency due to a classical component pathway complement deficiency
Expert Review Amber was added to C4A. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to C4A. Panel: Primary immunodeficiency disorders Phenotypes for gene C4A were set to C4a deficiency, Complement component 4 deficiency
Phenotypes for gene C4A were set to C4a deficiency
C4A was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
C4A was created by Louise Daugherty