Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: C2

The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 1:46 p.m. | Last Modified: 11 Mar 2026, 1:46 p.m.

Panel Version: 8.82

Green List (high evidence)

PMIDs: 32113979 and 34899688 report a total of seven C2 variants in seven cases of atypical hemolytic uremic syndrome. The variants are heterozygous with a gain-of-function mechanism.

Created: 16 Apr 2025, 5:03 p.m. | Last Modified: 16 Apr 2025, 5:03 p.m.

Panel Version: 7.27

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
C2 deficiency, OMIM:217000; complement component 2 deficiency, MONDO:0009006

Green List (high evidence)

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

• 34899688
• 32113979

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

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

Green List (high evidence)

Phenotypes
lupus

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): 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/A

Created: 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 dysfunction

Created: 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:8621452

Created: 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 immunodeficiency

Created: 1 Jun 2018, 12:04 p.m.

Comment on phenotypes: Added MIMid from OMIM and phenotype from Orphanet

Created: 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 deficiency

Created: 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: ENST00000299367

Created: 17 Apr 2018, 12:12 p.m.