Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: C2
In 34899688 and 32113979 shown that gain-of-function DOMINANT variants result in aHUS and C3-mediated glomerulopathy.Created: 3 Jun 2022, 6:15 a.m. | Last Modified: 3 Jun 2022, 6:15 a.m.
Panel Version: 2.550
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
aHUS and C3-mediated glomerulopathy
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
Phenotypes
lupus
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): C2 .PanelApp HGNC gene symbol check: C2 . IUIS Disease: C2 deficiency . IUIS Inheritance: AR .T cells: Low/variable, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: SLE, infections with encapsulated organisms, atherosclerosis. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/ACreated: 2 Jul 2018, 10:35 a.m.
Comment on phenotypes: Added phenotypes suggested from external expert review.Created: 13 Jun 2018, 1:39 p.m.
Comment on list classification: Changed from Amber to Green supporting immune dysfunctionCreated: 1 Jun 2018, 12:34 p.m.
Comment on publications: Added publications to support immune dysfunction in at least three unrelated cases. Complement C2 deficiency is the most common genetically determined complement deficiency with a prevalence estimated to be approximately 1:20,000 in individuals of Caucasian ancestry, making it a clinically important immune deficiency PMID:11079100,15643297. The deficiency is, in the majority of cases, caused by homozygosity for C2 genes having deletions in exon 6, resulting in complete absence of C2, or in some cases caused by other C2 gene mutations PMID:7901282 and PMID:8621452Created: 1 Jun 2018, 12:25 p.m.
Complement component 2 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiencyCreated: 1 Jun 2018, 12:04 p.m.
Comment on phenotypes: Added MIMid from OMIM and phenotype from OrphanetCreated: 1 Jun 2018, 11:57 a.m.
This gene was present in the original PanelApp PID panel dataset (review in April 2018) rated as Red. The gene is present in the 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: C2, PanelApp HGNC gene symbol check: C2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Complement component 2 deficiencyCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: C2, GRID_Gene_Symbol: C2, GRID_Transcript_ENS_Community submitted: ENST00000299367, GRID_Transcript_RefSeq: NM_000063.4, GRID_Transcript_ENS_used_on_Production: ENST00000299367Created: 17 Apr 2018, 12:12 p.m.
Source NHS GMS was added to C2.
Source North West GLH was added to C2.
Source London North GLH was added to C2.
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 C2 were set to Complement Component C2 Deficiency, C2 deficiency, 217000, Immunodeficiency due to C1, C4, or C2 component complement deficiency, Lupus, SLE, infections with encapsulated organisms, atherosclerosis, Complement Deficiencies
IUIS Classification February 2018 was added to C2. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to C2. Panel: Primary immunodeficiency disorders
Gene: c2 has been classified as Green List (High Evidence).
Phenotypes for gene: C2 were set to Complement Component C2 Deficiency; C2 deficiency, 217000; Immunodeficiency due to C1, C4, or C2 component complement deficiency; Lupus
Gene: c2 has been classified as Green List (High Evidence).
Publications for gene: C2 were set to 1577763; 8621452; 11079100; 15643297; 7901282
Phenotypes for gene: C2 were set to Complement Component C2 Deficiency; C2 deficiency, 217000; Immunodeficiency due to C1, C4, or C2 component complement deficiency
Phenotypes for C2 were set to Complement Component C2 Deficiency; C2 deficiency
Expert Review Amber was added to C2. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to C2. Panel: Primary immunodeficiency disorders Phenotypes for gene C2 were set to Complement Component C2 Deficiency, C2 deficiency, Complement component 2 deficiency
Phenotypes for gene C2 were set to Complement Component C2 Deficiency, C2 deficiency
GRID V2.0 was added to C2. Panel: Primary immunodeficiency disorders Phenotypes for gene C2 were set to Complement Component C2 Deficiency, C2 deficiency
C2 was added to Primary immunodeficiency disorders panel. Sources: Expert Review Red, Inherited complement deficiency v0.11
C2 was created by Louise Daugherty