Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: CD79A

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)

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): CD79A .PanelApp HGNC gene symbol check: CD79A . IUIS Disease: Iga deficiency . IUIS Inheritance: AR .T cells: Decreased or normal, response to PHA may be decreased, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Severe bacterial infections, normal numbers of pro-B cells. IUIS Major category: Predominantly Antibody Deficiencies. IUIS Subcategory: Severe Reduction in All Serum Immunoglobulin Isotypes with Profoundly Decreased or Absent B Cells, Agammaglobulinemia

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

Comment on list classification: Recent publication PMID: 29335801 (2018) supports the Amber to Green rating, and is the sixth patient with CD79a mutations described with CD79A deficiency.

Created: 4 May 2018, 4:35 p.m.

PMID: 29335801 supports the Amber to Green rating, and is the sixth patient with CD79A mutations described with CD79A deficiency.

Created: 4 May 2018, 4:34 p.m.

PMID: 29335801 (2018) CD79A (Igalpha) deficiency due to compound heterozygous mutations in the CD79A gene. Igα is the signal transduction molecule of the pre-B cell receptor. Absence of Igα results in a block from pro-B cells to pre-B cells in the B cell differentiation pathway, resulting in agammaglobulinemia (PMID:19302039). PMID: 29335801 (2018) describe a 16 year old male patient previously diagnosed with agammaglobulinemia due to CD79A (Igalpha) deficiency revealing a novel pathogenic insertion variant in the CD79A gene (NM_001783.3:c.353_354insT). Sequence analysis confirmed the diagnosis of CD79a deficiency due to compound heterozygous mutations: in one allele, and found the NM_001783.3:c.380-2A > G pathogenic variant as described previously (PMID:10525050); in the second allele, they found a novel insertion in exon 2 of a thymine (c.353insT). This variation creates a frame shift starting at p.(Cys119Leufs*63). The new reading frame ends in a STOP codon 63 positions downstream. This is the sixth patient with CD79A mutations described to date.

Created: 4 May 2018, 4:23 p.m.

The largest group of patients has X-linked agammaglobulinemia (XLA), which is a caused by a defect in the BTK gene encoding Bruton Tyrosine Kinsase (Btk), which accounts for 85% of agammaglobulinemia patients. A smaller group has defects in for instance IGLL1, CD79A, CD79B, or BLNK, which have clinical findings that are similar from those seen in patients with mutations in Btk but tend to have a more severe onset of disease. These were forms of agammaglobulinemia with autosomal recessive inheritance (ARA). All of these genes code for proteins that work with BTK to support the maturation of pro-B-cells into pre-B-cells. Patients with mutations in any of these genes have clinical and laboratory findings that are very similar to those seen in patients with mutations in BTK.

Created: 4 May 2018, 3:41 p.m.

Comment on publications: added additional publication as suggested by external reviewer- third homozygous LoF case report PMID: 24481606 (2014) and describes the fith case worldwide for autosomal recessive agammaglobulinemia due to a novel non-sense mutation in CD79a gene with a severe unusual onset due to an invasive central nervous system infection. The patient reported in PMID: 24481606 a novel defect in Igα presented with an unusual central nervous system infection that responded to treatment. The first reported patient with Igα deficiency presented in a Turkish family with prolonged and recurrent diarrhea, failure to thrive, bronchitis and neutropenia, all within the first year of life PMID:10525050. The second reported patient also was Turkish and showed an early onset form of immunodeficiency with recurrent lower respiratory tract infections and otitis media at 8 months and at 13 months she developed dermatomyositis PMID:11920841. Two patients with defects in extracellular domain also were reported in 2009 PMID:19302039.

Created: 4 May 2018, 3:06 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: CD79A, PanelApp HGNC gene symbol check: CD79A, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Agammaglobulinemias / Agammaglobulinemia

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

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CD79A, GRID_Gene_Symbol: CD79A, GRID_Transcript_ENS_Community submitted: ENST00000221972, GRID_Transcript_RefSeq: NM_001783.3, GRID_Transcript_ENS_used_on_Production: ENST00000221972

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

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)

Green List (high evidence)

Added ref to third homozygous LoF case report (24481606).

Created: 16 May 2017, 7:38 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• PMID: 24481606
• 11920841
• 10525050

Red List (low evidence)

ONly 2 cases ever described so probably needs a very careful review before clinical reporting!

Created: 6 Jan 2017, 3:14 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
agammaglobulinaemia

Comment when marking as ready: Two positve and one negative expert reviewers. Not associated with disease on Gen2PHen. Two homozygous LOF variants in publications.

Created: 11 May 2016, 10:36 a.m.