Activity
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| Cerebral vascular malformations v4.4 | CCER2 |
Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexandra Njegic, PMID:27717682 reported the identification of CCER2 variants in two pedigrees with Moyamoya disease. One of the monozygotic twins from family 2 with the missense variant was unaffected suggesting reduced penetrance. Although CCER2 variants were identified in three of 135 MMD probands additionally sequenced, two of them had RNF213 p.Arg4810Lys founder variant, and one had Graves disease. In silicon functional analysis predicts that these variants promote aggregation or oligomerization of their protein product. This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype. This gene should be rated amber with current evidence. |
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| Cerebral vascular malformations v3.29 | CBL |
Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexandra Njegic, there are five patients from three unrelated families reported with three different CBL variants and cerebral arteriopathy in PMID:32637631, and one patient was reported with the previously identified de novo splice variant in CBL gene in PMID:37778001. The patient from PMID:37778001 also had a maternally inherited VUS variant in RNF213 gene. This is also some functional evidence available. There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update. However, it has been tagged for expert review from the GMS. |
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| Cerebral vascular malformations v3.26 | CCER2 |
Alexandra Njegic gene: CCER2 was added gene: CCER2 was added to Cerebral vascular malformations. Sources: Literature Mode of inheritance for gene: CCER2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CCER2 were set to 27717682 Phenotypes for gene: CCER2 were set to Moyamoya Disease Penetrance for gene: CCER2 were set to Incomplete Mode of pathogenicity for gene: CCER2 was set to Other Review for gene: CCER2 was set to AMBER Added comment: 27717682: 2 pedigrees (without RNF213 variants), authors identified a delins and a missense variant (one twin unaffected with same missense variant, suggests reduced penetrance). Additional 135 MMD probands sequenced, identified 1 recurrent and an additional 2 in-frame indels (2 probands had RNF213 p.R4810K, and the other had Graves disease). In silico modelling predicts aggregation or oligomerization of CCER2 protein product; insufficient evidence to suggest LOF or GOF. Sources: Literature |
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| Cerebral vascular malformations v3.18 | SETD5 |
Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsAmber. Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only. NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only. NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene. |
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| Cerebral vascular malformations v3.18 | CNOT3 |
Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsAmber. Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene. |
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| Cerebral vascular malformations v3.18 | CHD4 |
Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsAmber. Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only. NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only. NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene. |
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| Cerebral vascular malformations v2.18 | RNF213 | Ivone Leong Phenotypes for gene: RNF213 were changed from {Moyamoya disease 2, susceptibility to} to {Moyamoya disease 2, susceptibility to}, OMIM:607151 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.70 | RNF213 | Louise Daugherty Publications for gene: RNF213 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.69 | RNF213 | Louise Daugherty Mode of inheritance for gene: RNF213 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.68 | RNF213 |
Louise Daugherty Source Expert Review Green was added to RNF213. Rating Changed from Red List (low evidence) to Green List (high evidence) |
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| Cerebral vascular malformations v1.67 | RNF213 | Louise Daugherty reviewed gene: RNF213: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.67 | RNF213 | Louise Daugherty Source Yorkshire and North East GLH was added to RNF213. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | RNF213 | Louise Daugherty Source NHS GMS was added to RNF213. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations | RNF213 | Ellen Thomas marked RNF213 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations | RNF213 | Alice Gardham reviewed RNF213 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||