Intellectual disability - microarray and sequencing
Gene: KDM2BThis gene is not currently associated with a disease phenotype in OMIM, but checked PMID:36322151 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tagCreated: 16 Oct 2023, 7:43 p.m. | Last Modified: 16 Oct 2023, 7:43 p.m.
Panel Version: 5.313
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.Created: 3 May 2023, 4:31 p.m. | Last Modified: 3 May 2023, 4:31 p.m.
Panel Version: 5.90
As reviewed by Mike Spiller (Sheffield Children's Hospital), 25 out of 27 patients (21/22 unrelated cases) reported in PMID:36322151 had developmental delay. Out of these, seven unrelated cases had intellectual disability (ranging from mild to severe) and four had global developmental delay among other clinical manifestations.Created: 3 May 2023, 4:22 p.m. | Last Modified: 3 May 2023, 4:22 p.m.
Panel Version: 5.86
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Publications
van Jaarsveld et al 2022 PMID: 36322151
Majority of variants are missense, strong evidence for hotspot in CXXC domain.(7 different de Novo missenses + 1 de Novo in frame del. Same inframe del also found de novo in NHS GMS patient. All absent from gnomAD, region highly constrained).
Also 3 LOF SNVs and 3 patients with deletions including this gene, although not all are de novo and most also have potential alternate causes.
All have developmental delay. Almost all have intellectual disability ranging from mild to moderate, speech delay common..7 with cardiac abnormalities, 4 with kidney abnormalities.
Also 2 variants published in this region in PMID: 35710456, 35904121.
KDM2B methylation episignature recorded. CXXC variants show strong clustering, highly distinct from control dataset. LOF variants (including dels) also reported to show distinct episignature from controls, and from CXXC variants. While the data supports a KDM2B LOF episignature, this is not as clear, and may not be as specific, as the CXXC signature.
Mouse model also supports importance of CXXC domain, with mice heterozygous for CXXC-deleted KDM2B showing neurological defects (PMID: 35128353).
Evidence very strong for CXXC missenses less clear for haploinsufficiency.
Overall sufficient evidence from cases and episignature evidence to include as green for ID.
Sources: LiteratureCreated: 25 Jan 2023, 3:53 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Tag gene-checked tag was added to gene: KDM2B.
Tag Q2_23_promote_green was removed from gene: KDM2B.
Source NHS GMS was added to KDM2B. Source Expert Review Green was added to KDM2B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Tag Q2_23_promote_green tag was added to gene: KDM2B.
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: KDM2B were changed from to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Publications for gene: KDM2B were set to 36322151
Publications for gene: KDM2B were set to PMID: 36322151; 35128353; 35710456
gene: KDM2B was added gene: KDM2B was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: KDM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KDM2B were set to PMID: 36322151; 35128353; 35710456 Review for gene: KDM2B was set to GREEN