Cerebral vascular malformations
Gene: CBLAfter NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The reviewers disagree with inclusion of this gene as there are only 2x variants reported to be associated with CVM on HGMD. A very strong possibility of incidental findings if variants only previously reported in association with JMML.Created: 30 Jan 2023, 4:01 p.m. | Last Modified: 30 Jan 2023, 4:01 p.m.
Panel Version: 2.68
This gene is associated with a phenotype in OMIM and Gene2Phenotype. Based on expert reviews and literature, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.Created: 3 Aug 2021, 9:17 a.m. | Last Modified: 3 Aug 2021, 9:17 a.m.
Panel Version: 2.57
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, 9:48 a.m. | Last Modified: 6 Jul 2021, 9:48 a.m.
Panel Version: 2.55
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563
Publications
New gene - deemed relevant to the GMS panel R336 Cerebral vascular malformationsCreated: 29 Nov 2019, 3:41 p.m. | Last Modified: 29 Nov 2019, 5:51 p.m.
Panel Version: 1.67
Comment on list classification: Changed rating from Red to Amber - this gene was deemed relevant to the GMS panel R336 Cerebral vascular malformations.
This was gene was recommended to be rated as Green but after further clinical expert it was decided to rate as Amber until there was sufficient evidence.Created: 29 Nov 2019, 3:36 p.m. | Last Modified: 29 Nov 2019, 5:51 p.m.
Panel Version: 1.67
Review from clinical expert (Vijeya Ganesan: GOSH / ICH): important association re leukaemia, green rating.Created: 29 Nov 2019, 3:35 p.m. | Last Modified: 29 Nov 2019, 3:35 p.m.
Panel Version: 1.53
The addition of the CBL gene is supported by two publication as well as personal observations of the submitter
Sources: Literature, ResearchCreated: 14 Apr 2019, 4:42 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
early-onset moyamoya angiopathy
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
Tag Q3_21_rating was removed from gene: CBL.
Tag Q3_21_rating tag was added to gene: CBL.
Phenotypes for gene: CBL were changed from early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, OMIM:613563 to early-onset moyamoya angiopathy; moyamoya disease, MONDO:0016820; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, OMIM:613563
Publications for gene: CBL were set to 28343148; 25283271
Phenotypes for gene: CBL were changed from early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563 to early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, OMIM:613563
Source Yorkshire and North East GLH was added to CBL.
Gene: cbl has been classified as Amber List (Moderate Evidence).
Source NHS GMS was added to CBL.
Gene: cbl has been classified as Green List (High Evidence).
Phenotypes for gene: CBL were changed from early-onset moyamoya angiopathy to early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563
gene: CBL was added gene: CBL was added to Cerebral vascular malformations. Sources: Literature,Research Mode of inheritance for gene: CBL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CBL were set to 28343148; 25283271 Phenotypes for gene: CBL were set to early-onset moyamoya angiopathy Penetrance for gene: CBL were set to Complete 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 Review for gene: CBL was set to GREEN