Cerebral vascular malformations
Gene: CNOT3The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.Created: 30 Jan 2023, 4:01 p.m. | Last Modified: 30 Jan 2023, 4:01 p.m.
Panel Version: 2.68
Updating tags to be Q3_22_expert_review and Q3_22_rating so that gene is included in the next GMS report (Oct 2022)Created: 5 Oct 2022, 11:13 p.m. | Last Modified: 5 Oct 2022, 11:13 p.m.
Panel Version: 2.60
After consultation with Helen Brittain (Clinical Fellow, Genomics England), SETD5 has been given an amber rating as the evidence of association was from a single publication. PMID: 31474762 reported CNOT3 variants in four unrelated cases of Intellectual developmental disorder with speech delay, autism, and dysmorphic facies (OMIM:618672), all of these cases had features of moyamoya disease.Created: 11 Oct 2022, 12:54 p.m. | Last Modified: 11 Oct 2022, 1:41 p.m.
Panel Version: 2.63
Comment on phenotypes: Moyamoya disease MONDO:0016820 is not specific to CNOT3 variants.Created: 11 Oct 2022, 11:52 a.m. | Last Modified: 11 Oct 2022, 11:52 a.m.
Panel Version: 2.62
Q2_21_expert_review added in order to ask whether the evaluation working group would like to seek specialist opinion on this gene / disease association.Created: 24 Jun 2021, 4:57 p.m. | Last Modified: 24 Jun 2021, 4:57 p.m.
Panel Version: 2.52
Comment on list classification: Associated with Intellectual developmental disorder with speech delay, autism, and dysmorphic facies (OMIM:618672) in OMIM and as confirmed Gen2Phen gene for CNOT3 syndrome. PMID 31474762 reports at least two de novo variants (one nonsense & one missense) in two cases with Moyamoya disease MONDO:0016820, who also had some of the features of OMIM:618672.
An association between CNOT3 protein levels, NTNG1 variants and cerebral atherosclorosis has also been reported in PMID 34073619.Created: 28 Apr 2021, 3:59 p.m. | Last Modified: 24 Jun 2021, 4:56 p.m.
Panel Version: 2.52
2 families with de novo variants (one nonsense and one missense) in individuals with ID and Moya Moya
Sources: LiteratureCreated: 9 Dec 2020, 7:04 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Moya Moya; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies, MIM# 618672
Publications
Tag Q3_22_rating was removed from gene: CNOT3. Tag Q3_22_expert_review was removed from gene: CNOT3.
Tag to_be_confirmed_NHSE tag was added to gene: CNOT3.
Tag Q3_22_expert_review tag was added to gene: CNOT3.
Tag Q3_22_expert_review was removed from gene: CNOT3.
Phenotypes for gene: CNOT3 were changed from Moyamoya disease MONDO:0016820; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672; intellectual developmental disorder with speech delay, autism, and dysmorphic facies MONDO:0032864 to Moyamoya disease MONDO:0016820; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672; intellectual developmental disorder with speech delay, autism, and dysmorphic facies MONDO:0032864
Tag Q2_21_expert_review was removed from gene: CNOT3. Tag Q3_22_rating tag was added to gene: CNOT3. Tag Q3_22_expert_review tag was added to gene: CNOT3.
Tag Q2_21_expert_review tag was added to gene: CNOT3.
Phenotypes for gene: CNOT3 were changed from Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672; intellectual developmental disorder with speech delay, autism, and dysmorphic facies MONDO:0032864 to Moyamoya disease MONDO:0016820; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672; intellectual developmental disorder with speech delay, autism, and dysmorphic facies MONDO:0032864
Gene: cnot3 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: CNOT3 were changed from Moya Moya; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies, MIM# 618672 to Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672; intellectual developmental disorder with speech delay, autism, and dysmorphic facies MONDO:0032864
gene: CNOT3 was added gene: CNOT3 was added to Cerebral vascular malformations. Sources: Literature Mode of inheritance for gene: CNOT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CNOT3 were set to 31474762 Phenotypes for gene: CNOT3 were set to Moya Moya; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies, MIM# 618672 Review for gene: CNOT3 was set to AMBER