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Primary immunodeficiency

Gene: MCM4

Green List (high evidence)

MCM4 (minichromosome maintenance complex component 4)
EnsemblGeneIds (GRCh38): ENSG00000104738
EnsemblGeneIds (GRCh37): ENSG00000104738
OMIM: 602638, Gene2Phenotype
MCM4 is in 5 panels

5 reviews

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

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

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Sarah Leigh (Genomics England Curator)

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.

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
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 1
Created: 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 supported
Created: 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 review
Created: 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 deficiency
Created: 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: ENST00000262105
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • Expert Review Green
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • 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
Tags
founder-effect
OMIM
602638
Clinvar variants
Variants in MCM4
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to MCM4.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to MCM4.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to MCM4.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

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.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

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

27 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: mcm4 has been classified as Green List (High Evidence).

27 Jun 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: MCM4 were set to 22354167; 22354170; 22499342; 16532402

27 Jun 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

27 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: mcm4 has been classified as Green List (High Evidence).

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to MCM4. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to MCM4. Panel: Primary immunodeficiency disorders

2 May 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

30 Apr 2018, Gel status: 2

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

30 Apr 2018, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for MCM4 were set to 22354167; 22354170

30 Apr 2018, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for MCM4 were set to Immunodeficiency 54 609981; Natural killer cell and glucocorticoid deficiency with DNA repair defect; Predisposition to several viral infection

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to MCM4. Panel: Primary immunodeficiency disorders

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

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

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene MCM4 were set to Natural killer cell and glucocorticoid deficiency with DNA repair defect

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

MCM4 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

MCM4 was created by Louise Daugherty