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Primary immunodeficiency

Gene: KMT2A

Amber List (moderate evidence)

KMT2A (lysine methyltransferase 2A)
EnsemblGeneIds (GRCh38): ENSG00000118058
EnsemblGeneIds (GRCh37): ENSG00000118058
OMIM: 159555, Gene2Phenotype
KMT2A is in 8 panels

4 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Upgraded from Red to Amber but there is enough evidence to promote to Green at the next GMS panel update.

Immune dysfunction, including early-onset CVID and recurrent infections, have been reported in multiple individuals with Wiedemann-Steiner syndrome. Immunopathology can be a presenting feature, and as there are sufficient unrelated cases with this phenotype, this gene should be promoted to Green.
Created: 29 Sep 2021, 11:52 a.m. | Last Modified: 29 Sep 2021, 11:52 a.m.
Panel Version: 2.475

Dmitrijs Rots (RadboudUMC)

Green List (high evidence)

Multiple individuals reported in the literature with hypogammaglobulinemia:
1) Two siblings in 28623346;
2) case in 27320412
3) Multiple individuals in a large review 33783954. "Thirteen participants completed immunology laboratory evaluations. Seven participants (53.8%) had abnormal immunoglobulin levels. Four participants (30.8%) had insufficient response to pneumococcal vaccinations. There were 18 participants (25.7%) with recurrent infections."
Therefore, immunological abnormaliteis and infections are common among WSS patients.
Additionally, KMT2A is included in IEI classification PMID: 31953710.
Created: 24 Sep 2021, 12:31 p.m. | Last Modified: 24 Sep 2021, 12:31 p.m.
Panel Version: 2.468

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypogammaglobulinemia; intellectual disability; hypertrichosis

Publications

Variants in this GENE are reported as part of current diagnostic practice

Sophie Hambleton (Newcastle University)

Red List (low evidence)

Poor evidence for any pathogenic link to immunodeficiency (single case report of immunodeficiency in a child with Wiedemann-Steiner syndrome and KMT2A mutation)
Created: 11 Jun 2018, 1:39 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Louise Daugherty (Genomics England Curator)

I don't know

Comment on mode of inheritance: Added MOI from external expert review
Created: 12 Jun 2018, 4:52 p.m.
Gene kept Red, external expert review supports Red status due to only one case reported, that has poor evidence for any pathogenic link to immunodeficiency.
Created: 12 Jun 2018, 4:46 p.m.
Comment on phenotypes: added phenotype from PMID: 27320412. Currently only one reported case in the literature with this observed phenotype caused by KMT2A
Created: 31 May 2018, 10:45 a.m.
Comment on publications: added publication to support PID phenotype. Missense variant reported.
Created: 31 May 2018, 10:44 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: 11q23, PanelApp HGNC gene symbol check: KMT2A, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Unclassified antibody deficiency / Unclassified antibody deficiency
Created: 17 Apr 2018, 12:29 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • IUIS Classification December 2019
  • ESID Registry 20171117
Phenotypes
  • Wiedemann-Steiner syndrome, OMIM:605130
Tags
Q3_21_rating
OMIM
159555
Clinvar variants
Variants in KMT2A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Sep 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: kmt2a has been classified as Amber List (Moderate Evidence).

29 Sep 2021, Gel status: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: KMT2A were set to 32048120; 27320412; 32086639

29 Sep 2021, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_21_rating tag was added to gene: KMT2A.

29 Sep 2021, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: KMT2A were changed from Wiedemann-Steiner syndrome with Congenital immunodeficiency; Unclassified antibody deficiency; Respiratory infections, short stature, hypertelorism, hairy elbows, developmental delay, intellectual disability; Combined immunodeficiencies with associated or syndromic features to Wiedemann-Steiner syndrome, OMIM:605130

28 Feb 2020, Gel status: 1

Added New Source, Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Source IUIS Classification December 2019 was added to KMT2A. Added phenotypes Respiratory infections, short stature, hypertelorism, hairy elbows, developmental delay, intellectual disability; Combined immunodeficiencies with associated or syndromic features for gene: KMT2A Publications for gene KMT2A were updated from 27320412 to 32048120; 27320412; 32086639

12 Jul 2018, Gel status: 1

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.

12 Jun 2018, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: KMT2A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

12 Jun 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: kmt2a has been classified as Red List (Low Evidence).

31 May 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: KMT2A were set to 27320412

31 May 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: KMT2A were set to Unclassified antibody deficiency; Wiedemann-Steiner syndrome with Congenital immunodeficiency

31 May 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: KMT2A were set to 27320412

31 May 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: KMT2A were set to 27320412

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

KMT2A was added to Primary immunodeficiency disorders panel. Sources: ESID Registry 20171117

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

KMT2A was created by Louise Daugherty