Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: C4A

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)

Complete C4 deficiency is associated with susceptibility to infection and predisposes to SLE

Created: 19 Jun 2018, 6:40 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
SLE predisposition; infections with encapsulated organisms

Publications

• 22482068

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): 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/A

Created: 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 association

Created: 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 susceptibility

Created: 15 Jun 2018, 4:20 p.m.

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

Created: 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 deficiency

Created: 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: ENST00000428956

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