Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: NCF4

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)

Please note 12 additional families reported July 2018.

Created: 12 Jul 2018, 4:21 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 29969437

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Very strong case for expecting loss of function to be pathogenic

Created: 29 Jun 2018, 2:49 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Red List (low evidence)

Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified as compound heterozygotes in one case. Supportive in vitro studies of patients' fibroblasts and expression studies of variant mRNA were presented (PMID 19692703).

Created: 2 May 2018, 1:18 p.m.

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

Comment on list classification: Changed Amber to Green from external review comment and further publication to support gene-disease association. van de Geer et al. (July 2018) PMID: 29969437 reported 24 patients from 12 families unrelated with bi-allelic mutations of the NCF4 gene, encoding the NADPH oxidase p40phox protein. Deficiency of p40phox is caused by homozygous (23 patients, 11 families) or compound heterozygous (one patient) mutations in families from eight countries.

Created: 13 Jul 2018, 8:59 a.m.

Comment on publications: Added recent publication suggested from external reviewer to support to Green rating

Created: 13 Jul 2018, 8:43 a.m.

Keep Amber until more info on gene and disease association. Although noted by expert review that this a very strong case for expecting loss of function to be pathogenic- there is currently no compelling functional information to support the rating being green given there is only one reported case to date. Request evidences / immunological association of this gene from GRID, GOSH and Victorian Clinical Genetics Services.

Created: 6 Jul 2018, 4:24 p.m.

Inactivating pathogenic variants in both NCF4 alleles were reported in one individual (PMID:19692703)

Created: 4 Jul 2018, 1:46 p.m.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency, mainly affecting phagocytes, which is characterized by an increased susceptibility to severe and recurrent bacterial and fungal infections, along with the development of granulomas.

Created: 4 Jul 2018, 1:32 p.m.

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): NCF4 .PanelApp HGNC gene symbol check: NCF4 . IUIS Disease: Autosomal recessive CGD p40phox . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N + M. IUIS Associated features: Infections, autoinflammatory phenotype. IUIS Major category: Congenital defects of phagocyte number or function. IUIS Subcategory: Defects of Respiratory Burst

Created: 2 Jul 2018, 10:35 a.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: P40-phox (NCF4), PanelApp HGNC gene symbol check: NCF4, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Phagocytic disorders / Chronic granulomatous disease (CGD) / Chronic granulomatous disease (CGD)

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: NCF4, GRID_Gene_Symbol: NCF4, GRID_Transcript_ENS_Community submitted: ENST00000397147, GRID_Transcript_RefSeq: NM_013416.3, GRID_Transcript_ENS_used_on_Production: ENST00000397147

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