Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: CR2

Green List (high evidence)

Comment on list classification: As reviewed by Hannah Knight, there are three unrelated cases in support of the association of CR2 to immunodeficiency. Hence, this gene can be promoted to Green in the next GMS review.

Created: 12 Oct 2023, 10:27 a.m. | Last Modified: 12 Oct 2023, 10:27 a.m.

Panel Version: 4.38

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Immunodeficiency, common variable, 7, OMIM:614699

Green List (high evidence)

One other report of this condition, not mentioned in reviews yet - PMID: 28499783 - two siblings from consanguineous parents, both with a homozygous frameshift variant in CR2

Created: 6 Oct 2023, 3:56 p.m. | Last Modified: 6 Oct 2023, 3:56 p.m.

Panel Version: 4.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency, common variable, 7

Publications

• 22035880
• 26325596
• 28499783

I don't know

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CR2 .PanelApp HGNC gene symbol check: CR2 . IUIS Disease: CD21 deficiency . IUIS Inheritance: AR .T cells: Low, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent infections. IUIS Major category: Predominantly Antibody Deficiencies. IUIS Subcategory: Severe Reduction in at Least 2 Serum Immunoglobulin Isotypes with Normal or Low Number of B Cells, CVID Phenotype

Created: 2 Jul 2018, 10:35 a.m.

Reviewed again and decided to keep as Amber, there are some conflict regarding the pertinence, still only two cases reported in the literature, and in addition to this, in Clinvar (July 2017) there are conflicting interpretations of pathogenicity reported in some clinical labs worldwide: Likely benign (Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine and ARUP Laboratories, Molecular Genetics and Genomics);Uncertain significance (Invitae), the gene-disease is not that strong.

Created: 9 May 2018, 12:36 p.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: CD21, PanelApp HGNC gene symbol check: CR2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Hypogammaglobulinemias / Common variable immunodeficiency disorders (CVID); Predominantly antibody disorders / Hypogammaglobulinemias / Isolated IgG subclass deficiency

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

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CR2, GRID_Gene_Symbol: CR2, GRID_Transcript_ENS_Community submitted: ENST00000367057, GRID_Transcript_RefSeq: NM_001006658.2, GRID_Transcript_ENS_used_on_Production: ENST00000367057

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

Green List (high evidence)

Red List (low evidence)

2 patients described only so caution required

Created: 6 Jan 2017, 3:18 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
hypogammaglobulinaemia

Publications

• 22035880
• 26325596

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal 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

Comment when marking as ready: One positive and one negative expert review. No disease associated on Gen2Phen. Two LOF variant identified in two compound heterozygotes.

Created: 11 May 2016, 9:39 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal