Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: PMS2The rating of this gene has been updated from Amber to Red following NHS Genomic Medicine Service approval.Created: 29 Jul 2022, 1:47 p.m. | Last Modified: 29 Jul 2022, 1:47 p.m.
Panel Version: 2.572
PMID: 30013564 suggests no PID phenotype among Constitutional MMR deficient cases. If monoallelic - risk for incidental findings.Created: 3 Jun 2022, 6:30 a.m. | Last Modified: 3 Jun 2022, 6:30 a.m.
Panel Version: 2.550
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Seems rarely to present as immunodeficiencyCreated: 29 Jun 2018, 3:03 p.m.
Comment on list classification: Associated with Mismatch repair cancer syndrome 276300 and Colorectal cancer, hereditary nonpolyposis, type 4 614337 in OMIM and as confirmed Gen2Phen gene for both of these phenotypes. At least 13 variants reported Mismatch repair cancer syndrome 276300 and 6 in Colorectal cancer, hereditary nonpolyposis, type 4 614337.Created: 9 May 2018, 12:37 p.m.
Comment on mode of inheritance: Monoallelic for Colorectal cancer, hereditary nonpolyposis, type 4 614337 and biallelic for Mismatch repair cancer syndrome 276300Created: 9 May 2018, 12:26 p.m.
Comment on phenotypes: Variants in PMS2 also associated with Colorectal cancer, hereditary nonpolyposis, type 4 614337Created: 9 May 2018, 12:22 p.m.
Keep Amber until more info on gene and disease association regarding immunological phenotype, external expert review denotes it rarely presents as immunodeficiencyCreated: 4 Jul 2018, 5:52 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): PMS2 .PanelApp HGNC gene symbol check: PMS2 . IUIS Disease: PMS2 Deficiency . IUIS Inheritance: AR .T cells: Poor activation, proliferation, motility, .B cells: Low B cells, switched and non-switched , .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent infections, caf-au-lait spots, lymphoma, colorectal carcinoma, brain tumors. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: DNA Repair Defects other than those listed in Table 1Created: 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: 20 Apr 2018, 12:25 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: PMS2, PanelApp HGNC gene symbol check: PMS2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / DNA-breakage disorder / Post-Meiotic Segregation 2 (PMS2) deficiency; Predominantly antibody disorders / Class switch recombination defects (CSR) / HIGM syndromes / CSR defects and Hyper IgM (HIGM) syndromesCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: PMS2, GRID_Gene_Symbol: PMS2, GRID_Transcript_ENS_Community submitted: ENST00000265849, GRID_Transcript_RefSeq: NM_000535.5, GRID_Transcript_ENS_used_on_Production: ENST00000265849Created: 17 Apr 2018, 12:12 p.m.
Source Expert Review Red was added to PMS2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Source IUIS Classification December 2019 was added to PMS2. Mode of inheritance for gene PMS2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Recurrent infections, cafe-au-lait spots, lymphoma, colorectal carcinoma, brain tumors; Combined immunodeficiencies with associated or syndromic features for gene: PMS2 Publications for gene PMS2 were updated from 7661930; 15077197; 9488480; 10763829; 16507833 to 15077197; 32048120; 7661930; 9488480; 16507833; 10763829; 32086639
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.
Gene: pms2 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene PMS2 were set to Mismatch repair cancer syndrome 276300, Post-Meiotic Segregation 2 (PMS2) deficiency, CSR defects and Hyper IgM (HIGM) syndromes, Recurrent infections, caf-au-lait spots, lymphoma, colorectal carcinoma, brain tumors, Combined immunodeficiencies with associated or syndromic features
IUIS Classification February 2018 was added to PMS2. Panel: Primary immunodeficiency disorders
This gene has been classified as Amber List (Moderate Evidence).
Publications for PMS2 were set to 7661930; 15077197; 9488480; 10763829; 16507833
Mode of inheritance for PMS2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for PMS2 were set to Mismatch repair cancer syndrome 276300; Post-Meiotic Segregation 2 (PMS2) deficiency; CSR defects and Hyper IgM (HIGM) syndromes
Expert Review Amber was added to PMS2. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to PMS2. Panel: Primary immunodeficiency disorders Phenotypes for gene PMS2 were set to Mismatch repair cancer syndrome, Post-Meiotic Segregation 2 (PMS2) deficiency, CSR defects and Hyper IgM (HIGM) syndromes
Phenotypes for gene PMS2 were set to Mismatch repair cancer syndrome
PMS2 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
PMS2 was created by Louise Daugherty