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Skeletal dysplasia

Gene: IDH2

Red List (low evidence)

IDH2 (isocitrate dehydrogenase (NADP(+)) 2, mitochondrial)
EnsemblGeneIds (GRCh38): ENSG00000182054
EnsemblGeneIds (GRCh37): ENSG00000182054
OMIM: 147650, Gene2Phenotype
IDH2 is in 12 panels

4 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

disorganized development of skeletal components gp of SD. Several het cases with 613657 - all codon R140. Het missense variants (codon R140). Mosaic variants in enchondromas/ metaphyseal chondromatosis - ? Test sensitivity.; Review on behalf of Tracy Lester
Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Enchondromatosis (Ollier) and Enchondromatosis with hermangiomata (Maffucci) 166000, metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (614875)

Publications

Mode of pathogenicity
Other - please provide details in the comments

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Keeping red for now. Associated with D-2-hydroxyglutaric aciduria 2 in OMIM but no skeletal phenotype. Also associated with somatic mosaic variants in patients with multiple enchondromas (Ollier disease) which can result in a skeletal phenotype.
Created: 11 Dec 2019, 6:06 p.m. | Last Modified: 11 Dec 2019, 6:06 p.m.
Panel Version: 1.287
Associated with D-2-hydroxyglutaric aciduria 2 #613657 in OMIM. No inheritance pattern given. Clinical features do not list skeletal characteristics.

PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G). Phenotypes of the patients are not given.

PMID: 24049096 - Nota et al. (2013) reported two patients with D-2-hydroxyglutaric aciduria-2, one in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo. In the other the mother also had mosacism for R140Q variant. No skeletal phenotypes are reported.

PMID: 22057234 - Pansuriya etal 2011 - state that 'Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). They report somatic heterozygous mutations IDH2 (c.516G>C encoding R172S) in enchondromas (benign cartilage tumors) and in spindle cell hemangiomas (benign vascular lesions).

Conclusion - associated with D-2-hydroxyglutaric aciduria but this does not have a skeletal phenotype. Also associated with somatic mutations which can result in Ollier disease and Maffucci syndrome
Created: 7 May 2019, 7:40 p.m. | Last Modified: 20 Nov 2019, 11:56 p.m.
Panel Version: 1.221
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: IDH2; Initial rating suggestion: Green - codon R140
Created: 6 Mar 2019, 11:36 a.m.

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Two variants reported in D-2-hydroxyglutaric aciduria 2 613657
Created: 13 Jul 2016, 8:58 a.m.
Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)
Created: 21 Jun 2016, 12:55 p.m.

Ana Beleza (Bristol Regional Genetics Service)

Green List (high evidence)

Tier 1
Created: 17 Jun 2016, 8:05 a.m.

Mode of inheritance
Unknown

Phenotypes
D-2-hydroxyglutaric aciduria 2 613657; Maffucci syndrome 614569; Ollier disease/ Dyschondroplasia 166000

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

Details

Mode of Inheritance
Unknown
Sources
  • Expert Review Red
  • NHS GMS
Phenotypes
  • Maffucci syndrome 614569
  • Enchondromatosis (Ollier) and Enchondromatosis with hermangiomata (Maffucci) 166000, metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (614875)
  • Ollier disease/ Dyschondroplasia 166000
  • D-2-hydroxyglutaric aciduria 2 613657
OMIM
147650
Clinvar variants
Variants in IDH2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

11 Dec 2019, Gel status: 1

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: idh2 has been classified as Red List (Low Evidence).

6 May 2019, Gel status: 1

Set Phenotypes, Set publications

Eleanor Williams (Genomics England Curator)

Added phenotypes Enchondromatosis (Ollier) and Enchondromatosis with hermangiomata (Maffucci) 166000, metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (614875) for gene: IDH2 Publications for gene IDH2 were changed from to 24049096; 22057234; 22057236

6 Mar 2019, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to IDH2.

9 Aug 2016, Gel status: 1

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to version 1 9th August 2016

13 Jul 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

13 Jul 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

13 Jul 2016, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for IDH2 were set to D-2-hydroxyglutaric aciduria 2 613657; Maffucci syndrome 614569; Ollier disease/ Dyschondroplasia 166000

7 Jul 2016, Gel status: 4

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for IDH2 was changed to Unknown

21 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

18 May 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

IDH2 was created by sleigh

18 May 2016, Gel status: 0

Added New Source

Sarah Leigh (Genomics England Curator)

IDH2 was added to Unexplained skeletal dysplasiapanel. Sources: