Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: TAP2

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)

Green List (high evidence)

Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.

Created: 14 Oct 2020, 4:40 p.m. | Last Modified: 14 Oct 2020, 4:40 p.m.

Panel Version: 2.322

The following PubMed IDs were added to gene TAP2 (OMIM gene MIM#170261): 20083708;7517574;10560675;11529920. These publications have been associated with the gene by the immunodeficiencies subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.

Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.

Panel Version: 2.208

Comment on list classification: More than 3 cases have been found where plausible disease causing mutations have been found in TAP2 in patients with Bare lymphocyte syndrome, type I/HLA-class I deficiency so changing the rating of this gene from Amber to Green.

Created: 9 May 2018, 1:36 p.m.

In OMIM TAP2 is associated with Bare lymphocyte syndrome, type I, due to TAP2 deficiency and Wegener-like granulomatosis. de la Salle et al. (1994) (PMID: 7517574) reported that in a family from Morocco with bare lymphocyte syndrome type I 2 of the 5 children were homozygous for an arg253-to-stop mutation in the TAP2 gene. Moins-Teisserenc et al (1999) (PMID: 10560675) report 5 patients with a syndrome of chronic necrotising granulomatous lesions, small-vessel vasculitis, recurrent respiratory-tract infections, and development of bronchiectasis. A diagnosis of Wegener's granulomatosis was considered for each. All 5 patients had a severe decrease in cell surface expression of HLA class I molecules and defective expression of the TAP complex. 2 patients (patients 1 and 3) were homozygous for a deletion of an adenosine (A) at codon 326, which caused a frameshift and a premature stop codon. The parents of patient 1 were heterozyous and symptom free. A PubMed search found 2 more publications associating TAP2 with Bare lymphocyte syndrome, type I/HLA-class I deficiency. Matamoros et al (2001) (PMID:11529920) report a 22 year old patient diagnosed with HLA-class I deficiency. The patient was found to have a homozygous single point mutation that results in a premature stop codon. España et al 2010 (PMID:20083708) report a patient with Bare Lymphocyte Syndrome and a severe reduction in HLA I expression in the patient's lymphocytes. The patient also developed squamous cell carcinoma. A TAP2 missense mutation was detected leading to a premature stop at codon. Her mother and daughters were heterozygous for the mutated allele. More than 3 cases have been found where plausible disease causing mutations have been found in TAP2 in patients with Bare lymphocyte syndrome, type I/HLA-class I deficiency so rating this gene Green.

Created: 9 May 2018, 1:34 p.m.

Comment on phenotypes: Added MIM number to Bare lymphocyte syndrome, type I, due to TAP2 deficiency and added Wegener-like granulomatosis

Created: 9 May 2018, 12:44 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 20083708
• 7517574
• 10560675
• 11529920

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): TAP2 .PanelApp HGNC gene symbol check: TAP2 . IUIS Disease: MHC class I deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Vasculitis, pyoderma gangrenosum. IUIS Major category: Immunodeficiencies affecting cellular and humoral immunity. IUIS Subcategory: Combined Immunodeficiencies Generally Less Profound than Severe Combined Immunodeficiency

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: 19 Apr 2018, 1:50 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: TAP2, PanelApp HGNC gene symbol check: TAP2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Combined immunodeficiencies / HLA class I deficiency / HLA class I deficiency

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

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TAP2, GRID_Gene_Symbol: TAP2, GRID_Transcript_ENS_Community submitted: ENST00000374899, GRID_Transcript_RefSeq: NM_000544.3, GRID_Transcript_ENS_used_on_Production: ENST00000374899

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