Ataxia and cerebellar anomalies - narrow panel
Gene: KCNA2
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.
Panel Version: 3.30
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least four variants reported in numberous cases, together with supportive functional studies, demonstrating GOF and LOF mechanisms.Created: 21 Apr 2021, 4 p.m. | Last Modified: 21 Apr 2021, 4 p.m.
Panel Version: 2.132
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 21 Apr 2021, 3:57 p.m. | Last Modified: 21 Apr 2021, 3:57 p.m.
Panel Version: 2.132
Comment on mode of pathogenicity: Both dominant negative variants that result in LOF effect (RCV000170511, rs786205231) and GOF variants (rs786205231, rs786205232) have been associated with Developmental and epileptic encephalopathy 32 OMIM:616366Created: 21 Apr 2021, 3:51 p.m. | Last Modified: 21 Apr 2021, 3:51 p.m.
Panel Version: 2.129
Ataxia is part of the phenotype.
Review of 23 affected individuals in PMID 29050392: some variants are LoF and others GoF, and some genotype-phenotype correlations made. The main differences were (i) predominant focal (loss-of-function) versus generalized (gain-of-function) seizures and corresponding epileptic discharges with prominent sleep activation in most cases with loss-of-function mutations; (ii) more severe epilepsy, developmental problems and ataxia, and atrophy of the cerebellum or even the whole brain in about half of the patients with gain-of-function mutations; and (iii) most severe early-onset phenotypes, occasionally with neonatal onset epilepsy and developmental impairment, as well as generalised and focal seizures and EEG abnormalities for patients with gain- and loss-of-function mutations.
Sources: Expert listCreated: 12 Sep 2020, 4:26 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Early infantile encephalopathy 32, MIM#616366
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_21_rating was removed from gene: KCNA2.
Source Expert Review Green was added to KCNA2. Source NHS GMS was added to KCNA2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: kcna2 has been classified as Amber List (Moderate Evidence).
Tag Q2_21_rating tag was added to gene: KCNA2.
Mode of pathogenicity for gene: KCNA2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Phenotypes for gene: KCNA2 were changed from Early infantile encephalopathy 32, MIM#616366 to Developmental and epileptic encephalopathy 32 OMIM:616366; developmental and epileptic encephalopathy, 32 MONDO:0014607
Mode of pathogenicity for gene: KCNA2 was changed from None to None
Publications for gene: KCNA2 were set to 29050392
gene: KCNA2 was added gene: KCNA2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list Mode of inheritance for gene: KCNA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNA2 were set to 29050392 Phenotypes for gene: KCNA2 were set to Early infantile encephalopathy 32, MIM#616366 Review for gene: KCNA2 was set to GREEN gene: KCNA2 was marked as current diagnostic