Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: TPP2Comment 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
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
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 familiesCreated: 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 LymphoproliferationCreated: 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 orphanetCreated: 27 Jun 2018, 4:38 p.m.
Comment on mode of inheritance: added MOI from external expert reviewCreated: 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: ENST00000376065Created: 17 Apr 2018, 12:12 p.m.
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
Gene: tpp2 has been classified as Green List (High Evidence).
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)
Source NHS GMS was added to TPP2.
Source North West GLH was added to TPP2.
Source London North GLH was added to TPP2.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Phenotypes for gene TPP2 were set 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
Gene: tpp2 has been classified as Green List (High Evidence).
Gene: tpp2 has been classified as Green List (High Evidence).
Phenotypes for gene: TPP2 were set to Tripeptidyl-Peptidase II Deficiency; TPP2 deficiency; Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome; immune thrombocytopenia and autoimmune hemolytic anemia; Evans syndrome
Phenotypes for gene: TPP2 were set to Tripeptidyl-Peptidase II Deficiency; TPP2 deficiency; Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome; immune thrombocytopenia and autoimmune hemolytic anemia
Phenotypes for gene: TPP2 were set to Tripeptidyl-Peptidase II Deficiency; TPP2 deficiency; Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome
Phenotypes for gene: TPP2 were set to TPP2 deficiency; Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome
Publications for gene: TPP2 were set to 25414442; 25525876
Publications for gene: TPP2 were set to 25414442; 25525876
Mode of inheritance for gene: TPP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
IUIS Classification February 2018 was added to TPP2. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to TPP2. Panel: Primary immunodeficiency disorders
This gene has been classified as Amber List (Moderate Evidence).
Phenotypes for gene TPP2 were set to TPP2 deficiency
TPP2 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
TPP2 was created by Louise Daugherty