Cerebral vascular malformations

Gene: CBL

Green List (high evidence)

CBL (Cbl proto-oncogene)
EnsemblGeneIds (GRCh38): ENSG00000110395
EnsemblGeneIds (GRCh37): ENSG00000110395
OMIM: 165360, Gene2Phenotype
CBL is in 14 panels

2 reviews

Natasha Brown (Victorian Clinical Genetics Services)

Green List (high evidence)

PMID: 28343148 two unrelated cases with de novo CBL variants in context of early onset severe bilateral moyamoya and subtle features of RASopathy but no haematological malignancy. One had het splice variant c.1228-2A>G previously demonstrated to lead to a partial or complete exon 9 deletion; another had het missense NM_005188.3:c.1111T>A; p.Tyr371Asn within the linker domain,
PMID: 25283271 - single case with Noonan like features, JMML, moyamoya and neovascular glaucoma.
PMID: 28589114 - single case presenting with atypical hemolytic uremic syndrome, moyamoya, and mild Noonan-like phenotype. Denovo heterozygous splicing variant in CBL (c.1096-1G>T)
Created: 6 Jul 2021, 6:09 a.m. | Last Modified: 6 Jul 2021, 6:09 a.m.
Panel Version: 0.19

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
moyamoya; cerebral arteriopathy

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Noonan syndrome-like disorder is a developmental disorder characterised by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, and ectodermal and musculoskeletal anomalies. Patients with heterozygous germline CBL mutations have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia. Over 20 affected individuals reported.
Created: 11 Sep 2020, 9:58 a.m. | Last Modified: 11 Sep 2020, 9:58 a.m.
Panel Version: 0.4327

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Noonan syndrome-like disorder with or without juvenile myelomonocytic leukaemia, MIM# 613563

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Expert Review Green
  • Genomics England PanelApp
  • Victorian Clinical Genetics Services
Phenotypes
  • early-onset moyamoya angiopathy
  • Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563
OMIM
165360
Clinvar variants
Variants in CBL
Penetrance
None
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

6 Jul 2021, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

6 Jul 2021, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: CBL were set to 25283271; 28343148

6 Jul 2021, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

18 May 2020, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: CBL was added gene: CBL was added to Cerebral vascular malformations. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: CBL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CBL were set to 25283271; 28343148 Phenotypes for gene: CBL were set to early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563 Mode of pathogenicity for gene: CBL was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments