Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: RANBP2

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 8:36 p.m. | Last Modified: 3 May 2024, 8:36 p.m.

Panel Version: 5.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Green List (high evidence)

Comment on list classification: As there are >3 unrelated cases reported with monoallelic variants in this gene, this gene can be promoted to green rating in the next GMS review.

Created: 4 Jan 2024, 10:09 a.m. | Last Modified: 4 Jan 2024, 10:09 a.m.

Panel Version: 4.134

In addition to the evidence provided by Dmitrijs Rots in his review, this gene has also been associated with relevant phenotypes in both OMIM (MIM #608033) and Gene2Phenotype (with 'limited' rating in the DD panel).

Created: 4 Jan 2024, 10:07 a.m. | Last Modified: 4 Jan 2024, 10:07 a.m.

Panel Version: 4.133

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{Encephalopathy, acute, infection-induced, 3, susceptibility to}, OMIM:608033

Green List (high evidence)

Included in IUIS 2022 inborn error of immunity disease list + multiple cases reported in the literature.

Created: 16 Oct 2022, 5:47 a.m. | Last Modified: 16 Oct 2022, 5:47 a.m.

Panel Version: 2.579

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• PMID: 35748970
• 25522933
• 29687329
• 30796099
• 35381605

Encephalopathy acute, infection induced susceptibility to, 3: 10 families, variable susceptibility to encephalopathy with infections - discuss penetrance and although there is an absence of primary immune dysfunction, whether this is a phenocopy like presentation? - Would a result be clinically useful?

Created: 26 Sep 2019, 3:59 p.m. | Last Modified: 26 Sep 2019, 3:59 p.m.

Panel Version: 1.130

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 only enough evidence to rate this gene Red

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 only enough evidence to rate this gene Red

Created: 26 Sep 2019, 3:35 p.m. | Last Modified: 26 Sep 2019, 3:35 p.m.

Panel Version: 1.127

Genes with discrepant ratings (PID 100K vs sumbmitted LNGLH submitted Immunology lists)--agreed rating in webex call 28 March 2019

Created: 26 Sep 2019, 3:34 p.m. | Last Modified: 26 Sep 2019, 3:34 p.m.

Panel Version: 1.127

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): RANBP2 .PanelApp HGNC gene symbol check: RANBP2 . IUIS Disease: Acute necrotizing encephalopathy . IUIS Inheritance: AD .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: Ubiquitous expression. IUIS Associated features: Fever induces acute encephalopathy. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Other Inborn Errors of Immunity Related to Non-Hematopoietic Tissues

Created: 6 Jul 2018, 12:34 p.m.