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Skeletal dysplasia v4.49 IDH2 Sarah Leigh Deleted their comment
Skeletal dysplasia v4.49 IDH2 Sarah Leigh Classified gene: IDH2 as Red List (low evidence)
Skeletal dysplasia v4.49 IDH2 Sarah Leigh Gene: idh2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v4.48 IDH2 Sarah Leigh changed review comment from: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.
This gene is rated as amber, because the variants are somatic, occurring in the tumour.; to: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.
This gene is rated as red, because the variants are somatic, occurring in the tumour.
Skeletal dysplasia v4.44 IDH2 Sarah Leigh Added comment: Comment on mode of inheritance: IDH2 variants associated with chondrosarcomas are somatic, occurring in the tumour material.
Skeletal dysplasia v4.44 IDH2 Sarah Leigh Mode of inheritance for gene: IDH2 was changed from Other to Other
Skeletal dysplasia v4.44 IDH2 Sarah Leigh Added comment: Comment on mode of inheritance: IDH2 variants associated with chondrosarcomas are somatic, occurring in the tumour material.
Skeletal dysplasia v4.44 IDH2 Sarah Leigh Mode of inheritance for gene: IDH2 was changed from Unknown to Other
Skeletal dysplasia v4.43 IDH2 Sarah Leigh changed review comment from: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.; to: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.
This gene is rated as amber, because the variants are somatic, occurring in the tumour.
Skeletal dysplasia v4.43 IDH2 Sarah Leigh edited their review of gene: IDH2: Changed rating: AMBER
Skeletal dysplasia v4.43 IDH2 Sarah Leigh Tag Q1_24_promote_green was removed from gene: IDH2.
Tag Q1_24_NHS_review was removed from gene: IDH2.
Tag somatic tag was added to gene: IDH2.
Skeletal dysplasia v4.41 IDH2 Sarah Leigh Classified gene: IDH2 as Amber List (moderate evidence)
Skeletal dysplasia v4.41 IDH2 Sarah Leigh Gene: idh2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.40 IDH2 Sarah Leigh Phenotypes for gene: IDH2 were changed from 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 to D-2-hydroxyglutaric aciduria 2, OMIM:613657; d-2-hydroxyglutaric aciduria 2, MONDO:0013345
Skeletal dysplasia v4.39 IDH2 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: IDH2.
Tag Q1_24_NHS_review tag was added to gene: IDH2.
Skeletal dysplasia v4.39 IDH2 Sarah Leigh edited their review of gene: IDH2: Added comment: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.; Changed rating: GREEN
Skeletal dysplasia v4.39 IDH2 Sarah Leigh Publications for gene: IDH2 were set to 24049096; 22057234; 22057236
Skeletal dysplasia v4.35 IDH2 Adrienne Flanagan reviewed gene: IDH2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 36042521; Phenotypes: Chondrosarcoma Conventional Central; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v4.35 TP53 Adrienne Flanagan gene: TP53 was added
gene: TP53 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TP53 were set to PMID: 33147331
Phenotypes for gene: TP53 were set to Central conventional chondrosrcoma
Review for gene: TP53 was set to GREEN
Added comment: Inactivating mutations in TP53 are common in dedifferentiated chondrosarcoma (DDCS) and, in a subset of cases, the TP53 mutation is restricted to the dedifferentiated nonchondrogenic component (8/11, 73% of the cases tested). Half of the tumours where the conventional chondrogenic component was paired with the high-grade non-chondrogenic component showed TP53 mutation in the chondrogenic area (3/6, 50%). These findings imply that TP53 alterations occur late in tumorigenesis, potentially with a TP53-mutant subclone that progresses to the dedifferentiated component in DDCS. Identification of TP53 mutation in an otherwise low-grade central chondrosarcoma may indicate the tumor is at increased risk of dedifferentiation.
Genetic testing for TP53 along with IDH1, IDH2 and TERT promoter mutations in central conventional chondrosarcoma could be useful in patient stratification.
Sources: Literature
Skeletal dysplasia v1.287 IDH2 Eleanor Williams Classified gene: IDH2 as Red List (low evidence)
Skeletal dysplasia v1.287 IDH2 Eleanor Williams Added comment: 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.
Skeletal dysplasia v1.287 IDH2 Eleanor Williams Gene: idh2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.221 IDH2 Eleanor Williams changed review comment from: 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).

PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo.

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; to: 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
Skeletal dysplasia v1.221 IDH2 Eleanor Williams changed review comment from: 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).

PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo.; to: 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).

PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo.

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
Skeletal dysplasia v1.154 IDH2 Eleanor Williams commented on gene: IDH2: 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).

PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo.
Skeletal dysplasia v1.153 IDH2 Eleanor Williams 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
Skeletal dysplasia v1.147 IDH2 Tracy Lester reviewed gene: IDH2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 22057236, 22057234, 24049096; Phenotypes: Enchondromatosis (Ollier) and Enchondromatosis with hermangiomata (Maffucci) 166000, metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (614875); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.146 IDH2 Eleanor Williams reviewed gene: IDH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.145 IDH2 Eleanor Williams Source NHS GMS was added to IDH2.