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22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) Loss
ISCA-37446-Loss 2
22q11.2 recurrent (DGS/VCFS) region (proximal, A-B) (includes TBX1) Loss
ISCA-37433-Loss 3

Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: TPP2

TPP2 (tripeptidyl peptidase 2)
EnsemblGeneIds (GRCh38): ENSG00000134900
EnsemblGeneIds (GRCh37): ENSG00000134900
OMIM: 190470, Gene2Phenotype
TPP2 is in 5 panels

5 reviews

Eleanor Williams (Genomics England Curator)

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, 4:43 p.m. | Last Modified: 14 Oct 2020, 4:43 p.m.

Panel Version: 2.327

The following PubMed IDs were added to gene TPP2 (OMIM gene MIM#190470): 25414442. These publications have been associated with the gene by the immunedysregulation 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

Publications

25414442

Created: 13 Oct 2020, 9:36 a.m.
Last Modified: 13 Oct 2020, 9:36 a.m.
Panel version: 2.208

Kimberly Gilmour (Great Ormond Street Hopsital)

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

Created: 17 Sep 2019, 3:18 p.m.
Last Modified: 17 Sep 2019, 3:18 p.m.
Panel version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

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

Created: 17 Sep 2019, 3:18 p.m.
Last Modified: 17 Sep 2019, 3:18 p.m.
Panel version: 1.94

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 20 Jun 2018, 11:07 p.m.

Panel version: 0.1158

Louise Daugherty (Genomics England Curator)

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

Personal correspondence has revealed 6 cases (5 confirmed genetically) in 3 unrelated families
Created: 2 Jul 2018, 12:42 p.m.

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TPP2 .PanelApp HGNC gene symbol check: TPP2 . IUIS Disease: Tripeptidyl-Peptidase II Deficiency . IUIS Inheritance: AR .T cells: Reduced, defective lymphocyte responses to anti-CD3, .B cells: Decreased , .IUIS Other affected cells: N/A. IUIS Associated features: Variable lymphoproliferation, severe autoimmune cytopenias, hypergammaglobulinemia, recurrent infections . IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Autoimmunity with or without Lymphoproliferation
Created: 2 Jul 2018, 10:35 a.m.

Comment on list classification: Changed Amber to Green from external expert review.
Created: 27 Jun 2018, 5:03 p.m.

Changed from Amber to Green, although there is no pathogenic variant reported in ClinVar, Stepensky et al. (2015) PMID:25414442 described two siblings that presented with Evans syndrome, viral infections, and progressive leukopenia. This also led to biochemical studies showing a broader principle governing the immune system: that intracellular amino acid homeostasis is inextricably linked, through aerobic glycolysis, to immune effector functions . The gene is rated Green by external expert review giving supportive evidence, and is on Victorian Clinical Genetics Services and GRID panels, so it was decided to rate this gene as green.
Created: 27 Jun 2018, 4:46 p.m.

Comment on phenotypes: added phenotype from orphanet
Created: 27 Jun 2018, 4:38 p.m.

Comment on mode of inheritance: added MOI from external expert review
Created: 27 Jun 2018, 4:30 p.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, 11:49 a.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TPP2, GRID_Gene_Symbol: TPP2, GRID_Transcript_ENS_Community submitted: ENST00000376065, GRID_Transcript_RefSeq: NM_003291, GRID_Transcript_ENS_used_on_Production: ENST00000376065
Created: 17 Apr 2018, 12:12 p.m.

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

Panel version: 1.94

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Other
NHS GMS
North West GLH
London North GLH
IUIS Classification February 2018
Victorian Clinical Genetics Services
GRID V2.0

Phenotypes

Tripeptidyl-Peptidase II Deficiency
TPP2 deficiency
Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome
immune thrombocytopenia and autoimmune hemolytic anemia
Evans syndrome
Variable lymphoproliferation, severe autoimmune cytopenias, hypergammaglobulinemia, recurrent infections
Diseases of Immune Dysregulation
Immunodeficiency 78 with autoimmunity and developmental delay, OMIM:619220

OMIM

190470

Clinvar variants

Variants in TPP2

Penetrance

None

Publications

Panels with this gene

History Filter Activity

10 Aug 2022, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TPP2 were changed from Tripeptidyl-Peptidase II Deficiency; TPP2 deficiency; Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome; immune thrombocytopenia and autoimmune hemolytic anemia; Evans syndrome; Variable lymphoproliferation, severe autoimmune cytopenias, hypergammaglobulinemia, recurrent infections; Diseases of Immune Dysregulation to Tripeptidyl-Peptidase II Deficiency; TPP2 deficiency; Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome; immune thrombocytopenia and autoimmune hemolytic anemia; Evans syndrome; Variable lymphoproliferation, severe autoimmune cytopenias, hypergammaglobulinemia, recurrent infections; Diseases of Immune Dysregulation; Immunodeficiency 78 with autoimmunity and developmental delay, OMIM:619220

14 Oct 2020, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tpp2 has been classified as Green List (High Evidence).

13 Oct 2020, Gel status: 1

Added New Source, Set publications, Status Update

Eleanor Williams (Genomics England Curator)

Source Other was added to TPP2. Publications for gene TPP2 were updated from 25414442; 25525876 to 25414442; 25525876 Rating Changed from Green List (high evidence) to Red List (low evidence)

17 Sep 2019, Gel status: 3