Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: PMS2

The 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

Red List (low evidence)

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

• 30013564

I don't know

Seems rarely to present as immunodeficiency

Created: 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 276300

Created: 9 May 2018, 12:26 p.m.

Comment on phenotypes: Variants in PMS2 also associated with Colorectal cancer, hereditary nonpolyposis, type 4 614337

Created: 9 May 2018, 12:22 p.m.

I don't know

Keep Amber until more info on gene and disease association regarding immunological phenotype, external expert review denotes it rarely presents as immunodeficiency

Created: 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 1

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: 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) syndromes

Created: 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: ENST00000265849

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