Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: KCNA2

Amber List (moderate evidence)

KCNA2 (potassium voltage-gated channel subfamily A member 2)
EnsemblGeneIds (GRCh38): ENSG00000177301
EnsemblGeneIds (GRCh37): ENSG00000177301
OMIM: 176262, Gene2Phenotype
KCNA2 is in 11 panels

2 reviews

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

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

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Developmental and epileptic encephalopathy 32 OMIM:616366
  • developmental and epileptic encephalopathy, 32 MONDO:0014607
Tags
Q2_21_rating
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

21 Apr 2021, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: kcna2 has been classified as Amber List (Moderate Evidence).

21 Apr 2021, Gel status: 0

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: KCNA2.

21 Apr 2021, Gel status: 0

Set mode of pathogenicity

Sarah Leigh (Genomics England Curator)

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

21 Apr 2021, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

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

21 Apr 2021, Gel status: 0

Set mode of pathogenicity

Sarah Leigh (Genomics England Curator)

Mode of pathogenicity for gene: KCNA2 was changed from None to None

21 Apr 2021, Gel status: 0

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: KCNA2 were set to 29050392

12 Sep 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

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