Ataxia and cerebellar anomalies - narrow panel
Gene: KCNA2

KCNA2 (potassium voltage-gated channel subfamily A member 2)
EnsemblGeneIds (GRCh38): ENSG00000177301
EnsemblGeneIds (GRCh37): ENSG00000177301
OMIM: 176262, Gene2Phenotype
KCNA2 is in 10 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

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

Created: 5 Feb 2023, 5:18 p.m.
Last Modified: 5 Feb 2023, 5:18 p.m.
Panel version: 3.30

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

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:616366
Created: 21 Apr 2021, 3:51 p.m. | Last Modified: 21 Apr 2021, 3:51 p.m.

Panel Version: 2.129

Created: 21 Apr 2021, 3:51 p.m.
Last Modified: 21 Apr 2021, 3:51 p.m.
Panel version: 2.132

Zornitza Stark (Australian Genomics)

Green List (high evidence)

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 list
Created: 12 Sep 2020, 4:26 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Early infantile encephalopathy 32, MIM#616366

Publications

29050392

Variants in this GENE are reported as part of current diagnostic practice

Created: 12 Sep 2020, 4:26 a.m.

Panel version: 2.12

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

NHS GMS
Expert Review Green

Phenotypes

Developmental and epileptic encephalopathy 32 OMIM:616366
developmental and epileptic encephalopathy, 32 MONDO:0014607

OMIM

176262

Clinvar variants

Variants in KCNA2

Penetrance

None

Publications

Mode of Pathogenicity

Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Panels with this gene

History Filter Activity

5 Feb 2023, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating was removed from gene: KCNA2.

5 Feb 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

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)

21 Apr 2021, Gel status: 2