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Early onset or syndromic epilepsy v3.93 | SEMA6B |
Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35604360 reported new unrelated cases identified with heterozygous variants in SEMA6B. Out of 16 patients referred for ID clinic, 10 of them had epilepsy or myoclonus. Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function. |
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Early onset or syndromic epilepsy v3.93 | SEMA6B | Achchuthan Shanmugasundram Publications for gene: SEMA6B were set to 32169168; 35604360 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.92 | SEMA6B |
Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35604360 reported new unrelated cases identified with heterozygous variants in SEMA6B. Out of 16 patients referred for ID clinic, 10 of them had epilepsy or myoclonus. Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function. |
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Early onset or syndromic epilepsy v3.92 | SEMA6B | Achchuthan Shanmugasundram Publications for gene: SEMA6B were set to 32169168; 35604360 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.92 | SEMA6B |
Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35604360 reported new unrelated cases identified with heterozygous variants in SEMA6B. Out of 16 patients referred for ID clinic, 10 of them had epilepsy or myoclonus. Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function. |
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Early onset or syndromic epilepsy v3.92 | SEMA6B | Achchuthan Shanmugasundram Publications for gene: SEMA6B were set to 32169168 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.491 | SEMA6B | Sarah Leigh Tag for-review was removed from gene: SEMA6B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.491 | SEMA6B | Sarah Leigh commented on gene: SEMA6B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.490 | SEMA6B |
Sarah Leigh Source Expert Review Green was added to SEMA6B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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Early onset or syndromic epilepsy v2.285 | SEMA6B | Sarah Leigh Phenotypes for gene: SEMA6B were changed from Epilepsy, progressive myoclonic, 11, 618876 to Epilepsy, progressive myoclonic, 11 OMIM:618876 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.281 | SEMA6B | Helen Lord reviewed gene: SEMA6B: Rating: AMBER; Mode of pathogenicity: None; Publications: 32169168; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.186 | SEMA6B | Arina Puzriakova Classified gene: SEMA6B as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.186 | SEMA6B | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.186 | SEMA6B | Arina Puzriakova Gene: sema6b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.181 | SEMA6B | Arina Puzriakova Tag for-review tag was added to gene: SEMA6B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.80 | SEMA6B | Rebecca Foulger changed review comment from: Comment on list classification: Added to panel and rated Green by Zornitza Stark. Sufficient cases with seizure phenotype in PMID:32169168 plus mouse model. Not yet associated with a disorder in G2P but relevant OMIM phenotype.; to: Comment on list classification: Gene was added to panel and rated Green by Zornitza Stark. Sufficient cases with seizure phenotype in PMID:32169168 plus mouse model. Not yet associated with a disorder in G2P but relevant OMIM phenotype. Therefore updated rating from Grey to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.80 | SEMA6B | Rebecca Foulger Classified gene: SEMA6B as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.80 | SEMA6B | Rebecca Foulger Added comment: Comment on list classification: Added to panel and rated Green by Zornitza Stark. Sufficient cases with seizure phenotype in PMID:32169168 plus mouse model. Not yet associated with a disorder in G2P but relevant OMIM phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.80 | SEMA6B | Rebecca Foulger Gene: sema6b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.79 | SEMA6B | Rebecca Foulger Added comment: Comment on mode of pathogenicity: The authors of PMID:32169168 suggest a dominant-negative or gain-of-function effect rather than haploinsufficiency. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.79 | SEMA6B | Rebecca Foulger Mode of pathogenicity for gene: SEMA6B was changed from None to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.78 | SEMA6B | Rebecca Foulger changed review comment from: PMID:32169168. In 4 unrelated patients (2 Japanese, ISraeli and Malaysian) with progressive myoclonic epilepsy, Hamanaka et al. (2020) identified de novo heterozygous frameshift mutations in the last exon of the SEMA6B gene. Variants were predicted to result in truncated proteins. Truncating variants in this region of the gene were not observed in the gnomAD database, although truncating variants in other regions of the gene were observed in gnomAD. The authors postulated a dominant-negative or gain-of-function effect rather than haploinsufficiency. In an animal model, the authors found that zebrafish with truncating sema6b variants were more susceptible to seizures.; to: PMID:32169168. In 4 unrelated patients (2 Japanese, 1 Israeli and 1 Malaysian) with progressive myoclonic epilepsy, Hamanaka et al. (2020) identified de novo heterozygous frameshift mutations in the last exon of the SEMA6B gene. Variants were predicted to result in truncated proteins. Truncating variants in this region of the gene were not observed in the gnomAD database, although truncating variants in other regions of the gene were observed in gnomAD. The authors postulated a dominant-negative or gain-of-function effect rather than haploinsufficiency. In an animal model, the authors found that zebrafish with truncating sema6b variants were more susceptible to seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.78 | SEMA6B | Rebecca Foulger commented on gene: SEMA6B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.78 | SEMA6B | Rebecca Foulger Phenotypes for gene: SEMA6B were changed from Progressive myoclonic epilepsy to Epilepsy, progressive myoclonic, 11, 618876 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.38 | SEMA6B |
Zornitza Stark gene: SEMA6B was added gene: SEMA6B was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: SEMA6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SEMA6B were set to 32169168 Phenotypes for gene: SEMA6B were set to Progressive myoclonic epilepsy Review for gene: SEMA6B was set to GREEN Added comment: Five individuals from unrelated families reported with de novo variants in the last exon, escaping NMD. Sources: Literature |