**Note: In September 2021, the ClinGen Epilepsy GCEP opted to change the disease term on this curation from generalised epilepsy to epilepsy. The evidence summary below reflects this change. The original evidence and conclusion remains the same; therefore, the original date of approval has not been changed. **
Variants in the CHRNA2 gene has been reported in 4 affected individuals with autosomal dominant Idiopathic epilepsy since 2011 (Klassen et al.). Four unique variants (two missense, one nonsense, one frameshift) have been reported. The two missense variants were not proved to affect the protein function yet and one frameshift variant was also observed in unaffected father. One nonsense variant was also observed in general population database (gnomAD). The variant in this gene was identified by NGS panel testing. In summary, there is no scored evidence to support the CHRNA2 and idiopathic epilepsy association. This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel by 1/7/2020.
Lumping and Splitting: Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in phenotypic variability between three disease entities: (1) Nocturnal frontal lobe epilepsy (MONDO:0000030), (2) Idiopathic epilepsy (MONDO:0005579) and (3) Benign familial infantile seizure (MONDO:0011140). Therefore, we have split curations for the disease entities, (1) Nocturnal frontal lobe epilepsy (MONDO:0000030), (2) Idiopathic epilepsy (MONDO:0005579) and (3) Benign familial infantile seizure (MONDO:0011140).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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