| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Familial Generalised Epilepsy v0.14 | USP25 | Zornitza Stark Marked gene: USP25 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.14 | USP25 | Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.14 | USP25 | Zornitza Stark Classified gene: USP25 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.14 | USP25 | Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.13 | USP25 |
Sangavi Sivagnanasundram gene: USP25 was added gene: USP25 was added to Familial Generalised Epilepsy. Sources: Other Mode of inheritance for gene: USP25 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: USP25 were set to 38875478 Phenotypes for gene: USP25 were set to USP25-related epilepsy (epilepsy, idiopathic generalized, MONDO:0005579) Mode of pathogenicity for gene: USP25 was set to Other Review for gene: USP25 was set to GREEN Added comment: PMID: 38875478 5 heterozygous variants were identified in 8 individuals from 5 unrelated families all with clinical phenotypes associated with generalised epilepsy and/or febrile seizures. Knock-out mouse model showed increased seizure susceptibility compared to the WT. Both loss of function and gain of function variants can be a mechanism of disease in individuals with USP25-related epilepsy. Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.13 |
Zornitza Stark HPO terms changed from to Seizure, HP:0001250 List of related panels changed from to Seizure; HP:0001250 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.12 | Bryony Thompson Panel status changed from internal to public | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.11 | SCN9A | Bryony Thompson Marked gene: SCN9A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.11 | SCN9A | Bryony Thompson Gene: scn9a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.11 | SCN9A | Bryony Thompson Classified gene: SCN9A as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.11 | SCN9A | Bryony Thompson Added comment: Comment on list classification: ClinGen Epilepsy GCEP curated gene-disease association with epilepsy: A novel publication provides evidence against pathogenicity for a previously reported variant providing the primary evidence for an association with epilepsy. Classification - 03/09/2021 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.11 | SCN9A | Bryony Thompson Gene: scn9a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.10 | CPA6 | Bryony Thompson Marked gene: CPA6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.10 | CPA6 | Bryony Thompson Gene: cpa6 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.10 | CPA6 | Bryony Thompson Classified gene: CPA6 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.10 | CPA6 |
Bryony Thompson Added comment: Comment on list classification: ClinGen Epilepsy GCEP has reviewed both inheritances for gene-disease associations with epilepsy: AR disease is Disputed - There is contradictory case level and experimental data regarding any association between CPA6 and autosomal recessive epilepsy. Classification - 07/29/2021 AD disease is Refuted- There is very limited evidence supporting a gene-disease association. Many of the reported pathogenic variants have been subsequently identified as having a high minor allele frequency in population databases. Classification - 07/29/2021 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.10 | CPA6 | Bryony Thompson Gene: cpa6 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.9 | CNTN2 | Bryony Thompson Marked gene: CNTN2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.9 | CNTN2 | Bryony Thompson Gene: cntn2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.9 | CNTN2 | Bryony Thompson Publications for gene: CNTN2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.8 | CNTN2 | Bryony Thompson Mode of inheritance for gene: CNTN2 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.7 | CNTN2 | Bryony Thompson Classified gene: CNTN2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.7 | CNTN2 | Bryony Thompson Gene: cntn2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.6 | CNTN2 | Bryony Thompson reviewed gene: CNTN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23518707, 34120799, 34691156; Phenotypes: Epilepsy, myoclonic, familial adult, 5 MIM#615400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.6 | CASR | Bryony Thompson Marked gene: CASR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.6 | CASR | Bryony Thompson Gene: casr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.6 | CASR | Bryony Thompson Classified gene: CASR as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.6 | CASR | Bryony Thompson Added comment: Comment on list classification: Disputed epilepsy gene-disease association, curated by ClinGen epilepsy GCEP, Classification - 03/03/2021 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.6 | CASR | Bryony Thompson Gene: casr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.5 | CACNB4 | Bryony Thompson Classified gene: CACNB4 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.5 | CACNB4 | Bryony Thompson Added comment: Comment on list classification: Disputed epilepsy gene, curated by ClinGen Epilepsy Gene Curation Expert Panel - Classification - 06/22/2018 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.5 | CACNB4 | Bryony Thompson Gene: cacnb4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.4 | CASR | Bryony Thompson Deleted their review | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.4 | CASR | Bryony Thompson Classified gene: CASR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.4 | CASR | Bryony Thompson Gene: casr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.3 | CASR | Bryony Thompson Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.3 | CASR | Bryony Thompson Classified gene: CASR as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.3 | CASR | Bryony Thompson Added comment: Comment on list classification: Disputed epilepsy gene - assessed by ClinGen Epilepsy GCEP - Classification - 06/22/2018 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.3 | CASR | Bryony Thompson Gene: casr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.2 | Bryony Thompson Panel types changed to Royal Melbourne Hospital | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | TRAK1 |
Bryony Thompson gene: TRAK1 was added gene: TRAK1 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: TRAK1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TRAK1 were set to Epileptic encephalopathy, early infantile, 68 618201 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | SLC2A1 |
Bryony Thompson gene: SLC2A1 was added gene: SLC2A1 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: SLC2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: SLC2A1 were set to {Epilepsy, idiopathic generalized, susceptibility to, 12} 614847 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | SCN9A |
Bryony Thompson gene: SCN9A was added gene: SCN9A was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: SCN9A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SCN9A were set to {Dravet syndrome, modifier of} 607208; Epilepsy, generalized, with febrile seizures plus, type 7 613863; Febrile seizures, familial, 3B 613863 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | SCN2A |
Bryony Thompson gene: SCN2A was added gene: SCN2A was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SCN2A were set to Seizures, benign familial infantile, 3 607745; Epileptic encephalopathy, early infantile, 11 613721 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | SCN1B |
Bryony Thompson gene: SCN1B was added gene: SCN1B was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: SCN1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: SCN1B were set to Epileptic encephalopathy, early infantile, 52 617350 AR; Epilepsy, generalized, with febrile seizures plus, type 1 604233 AD |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | SCN1A |
Bryony Thompson gene: SCN1A was added gene: SCN1A was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SCN1A were set to Epileptic encephalopathy, early infantile, 6 (Dravet syndrome) 607208; Epilepsy, generalized, with febrile seizures plus, type 2 604403 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | PRRT2 |
Bryony Thompson gene: PRRT2 was added gene: PRRT2 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: PRRT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: PRRT2 were set to Episodic kinesigenic dyskinesia 1; Seizures, benign familial infantile, 2; Convulsions, familial infantile, with paroxysmal choreoathetosis |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | PCDH19 |
Bryony Thompson gene: PCDH19 was added gene: PCDH19 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: PCDH19 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: PCDH19 were set to Epileptic encephalopathy, early infantile, 9 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | NEDD4L |
Bryony Thompson gene: NEDD4L was added gene: NEDD4L was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: NEDD4L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: NEDD4L were set to Periventricular nodular heterotopia 7, 617201 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | LGI1 |
Bryony Thompson gene: LGI1 was added gene: LGI1 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: LGI1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: LGI1 were set to Epilepsy, familial temporal lobe, 1 600512 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | KCNQ3 |
Bryony Thompson gene: KCNQ3 was added gene: KCNQ3 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: KCNQ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: KCNQ3 were set to Seizures, benign neonatal, type 2 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | KCNMA1 |
Bryony Thompson gene: KCNMA1 was added gene: KCNMA1 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: KCNMA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: KCNMA1 were set to Generalized epilepsy-paroxysmal dyskinesia syndrome, MONDO:0012276; Epilepsy, idiopathic generalized, susceptibility to, 16, MONDO:0032827; Cerebellar atrophy, developmental delay, and seizures, OMIM:617643 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | GABRG2 |
Bryony Thompson gene: GABRG2 was added gene: GABRG2 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: GABRG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: GABRG2 were set to {Epilepsy, childhood absence, susceptibility to, 2} 607681; Epilepsy, generalized, with febrile seizures plus, type 3 611277 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | GABRB3 |
Bryony Thompson gene: GABRB3 was added gene: GABRB3 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: GABRB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: GABRB3 were set to Epilepsy, childhood absence, susceptibility to, 5 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | GABRA1 |
Bryony Thompson gene: GABRA1 was added gene: GABRA1 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: GABRA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: GABRA1 were set to {Epilepsy, childhood absence, susceptibility to, 4} 611136 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | DEPDC5 |
Bryony Thompson gene: DEPDC5 was added gene: DEPDC5 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: DEPDC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: DEPDC5 were set to Epilepsy, familial focal, with variable foci 1, OMIM:604364 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | CPA6 |
Bryony Thompson gene: CPA6 was added gene: CPA6 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: CPA6 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: CPA6 were set to Epilepsy, familial temporal lobe, 5 614417 AR, AD; Febrile seizures, familial, 11 614418 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | CNTN2 |
Bryony Thompson gene: CNTN2 was added gene: CNTN2 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: CNTN2 was set to Phenotypes for gene: CNTN2 were set to Epilepsy, familial adult myoclonic, 5 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | CASR |
Bryony Thompson gene: CASR was added gene: CASR was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: CASR was set to Phenotypes for gene: CASR were set to {Epilepsy idiopathic generalized, susceptibility to, 8}, 612899 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | CACNB4 |
Bryony Thompson gene: CACNB4 was added gene: CACNB4 was added to Familial Generalised Epilepsy. Sources: Expert Review Green,GREP Mode of inheritance for gene: CACNB4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: CACNB4 were set to {Epilepsy, idiopathic generalized, susceptibility to, 9} OMIM:607682 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial Generalised Epilepsy v0.0 | Bryony Thompson Added panel Familial Generalised Epilepsy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||