Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: MCM4Comment on list classification: Gene was reassessed following a recent Amber review by Zornitza Stark. Although there has only been a single founder variant reported to date, the rating was based on multiple Green GMS expert reviews and the functional support was deemed sufficiently compelling. Therefore, the Green gene rating will be maintained on this panel.Created: 13 Aug 2021, 11:20 a.m. | Last Modified: 13 Aug 2021, 11:20 a.m.
Panel Version: 2.458
More than 20 individuals, within Irish Traveller community reported with a single homozygous variant, founder effect demonstrated (c.71-1insG resulting in a severely truncated protein (p.Pro24ArgfsX4)).
No other variants reported.Created: 5 Aug 2021, 8:58 a.m. | Last Modified: 5 Aug 2021, 8:58 a.m.
Panel Version: 2.452
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Immunodeficiency 54, MIM# 609981
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
Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. One variant identified in at least 5 consanguineous Irish Traveller kindreds with Natural killer cell and glucocorticoid deficiency with DNA repair defect. Patients had decreased numbers of CD56(dim) natural killer (NK) cells, indicating a defect in NK cell differentiation (PMID 22354167)Created: 30 Apr 2018, 4:19 p.m.
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): MCM4 .PanelApp HGNC gene symbol check: MCM4 . IUIS Disease: MCM4 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: NK cells: low number and function. Viral infections (EBV, HSV, VZV), short stature, B cell lymphoma, adrenal failure . 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.
Comment on publications: added further publications PMID: 22499342;16532402 to support pathogenic variant. As there are number of cases, with additional functional support for the variant itself after internal clinical review Green rating was supportedCreated: 27 Jun 2018, 4:07 p.m.
added founder-tag. Only one pathogenic variant reported in Irish Traveller kindreds. In view of expert review Green and functional info this gene was made Green.Created: 27 Jun 2018, 4:03 p.m.
Comment on list classification: Changed Amber to Green from external expert reviewCreated: 27 Jun 2018, 3:59 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: 20 Apr 2018, 12:25 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: MCM4, PanelApp HGNC gene symbol check: MCM4, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Defects in innate immunity / Predisposition to several viral infection / Predisposition to several viral infection; Other well defined PIDs / DNA-breakage disorder / MCM4 deficiencyCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: MCM4, GRID_Gene_Symbol: MCM4, GRID_Transcript_ENS_Community submitted: ENST00000262105, GRID_Transcript_RefSeq: NM_005914.3, GRID_Transcript_ENS_used_on_Production: ENST00000262105Created: 17 Apr 2018, 12:12 p.m.
Gene: mcm4 has been classified as Green List (High Evidence).
Source NHS GMS was added to MCM4.
Source North West GLH was added to MCM4.
Source London North GLH was added to MCM4.
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 MCM4 were set to Immunodeficiency 54, 609981, Natural killer cell and glucocorticoid deficiency with DNA repair defect, Predisposition to several viral infection, MCM4 deficiency, NK cells: low number and function. Viral infections (EBV, HSV, VZV), short stature, B cell lymphoma, adrenal failure, Combined immunodeficiencies with associated or syndromic features
Gene: mcm4 has been classified as Green List (High Evidence).
Publications for gene: MCM4 were set to 22354167; 22354170; 22499342; 16532402
Phenotypes for gene: MCM4 were set to Immunodeficiency 54, 609981; Natural killer cell and glucocorticoid deficiency with DNA repair defect; Predisposition to several viral infection; MCM4 deficiency
Gene: mcm4 has been classified as Green List (High Evidence).
IUIS Classification February 2018 was added to MCM4. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to MCM4. Panel: Primary immunodeficiency disorders
Phenotypes for MCM4 were set to Immunodeficiency 54 609981; Natural killer cell and glucocorticoid deficiency with DNA repair defect; Predisposition to several viral infection; MCM4 deficiency
This gene has been classified as Amber List (Moderate Evidence).
Publications for MCM4 were set to 22354167; 22354170
Phenotypes for MCM4 were set to Immunodeficiency 54 609981; Natural killer cell and glucocorticoid deficiency with DNA repair defect; Predisposition to several viral infection
Expert Review Amber was added to MCM4. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to MCM4. Panel: Primary immunodeficiency disorders Phenotypes for gene MCM4 were set to Natural killer cell and glucocorticoid deficiency with DNA repair defect, Predisposition to several viral infection, MCM4 deficiency
Phenotypes for gene MCM4 were set to Natural killer cell and glucocorticoid deficiency with DNA repair defect
MCM4 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
MCM4 was created by Louise Daugherty