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Intellectual disability

Gene: KCNN2

Amber List (moderate evidence)

KCNN2 (potassium calcium-activated channel subfamily N member 2)
EnsemblGeneIds (GRCh38): ENSG00000080709
EnsemblGeneIds (GRCh37): ENSG00000080709
OMIM: 605879, Gene2Phenotype
KCNN2 is in 2 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: New gene added by Zornitza Stark. There is enough evidence to promote this gene to Green at the next GMS panel update - variable degrees of cognitive impairment were a universal feature amongst individuals with KCNN2 variants (at least 10 unrelated cases with unique variants). Pathogenicity was supported by functional data.
Created: 10 Feb 2021, 1:58 p.m. | Last Modified: 10 Feb 2021, 1:58 p.m.
Panel Version: 3.777
- PMID: 33242881 (2020) - 10 patients with de novo KCNN2 variants and one individual with a heterozygous missense variant inherited from an affected parent, detected by WES. Patch-clamp functional studies showed that all but one variant (p.Glu30Gln) tested, which was reclassified VUS, led to to a loss-of-function of SK2 channels.

Excluding the case with the VUS, one patient displayed DD, 4 patients exhibited mild ID, 3 patients had moderate ID, and 2 had severe ID. Other clinical characteristics include a movement disorder (6/10) including tremor (5), cerebellar ataxia (4), and extrapyramidal symptoms (4); epilepsy (2/10); white matter abnormalities (3/6). Authors note that the 4 individuals without a movement disorder were under the age of 16 years at the time of the study and there is a possibility that this manifestation may arise later in life.
Created: 10 Feb 2021, 1:54 p.m. | Last Modified: 10 Feb 2021, 1:54 p.m.
Panel Version: 3.776

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

- 11 probands all de novo except for 1 mother-daughter pair.
- a mix of null and missense variants
- 2/11 with microcephaly, 10/11 motor delay, 7/11 language delay (excluding 2 with regression), all with varying degrees of ID, 3/11 seizures, 7/11 movement disorder, 4/11 cerebellar ataxia, 6/11 MRI anomalies
Sources: Literature
Created: 1 Feb 2021, 9:18 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability; seizures; movement disorder

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
  • Intellectual disability
  • seizures
  • movement disorder
Tags
Q2_21_rating
OMIM
605879
Clinvar variants
Variants in KCNN2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

10 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: kcnn2 has been classified as Amber List (Moderate Evidence).

10 Feb 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: KCNN2.

1 Feb 2021, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: KCNN2 was added gene: KCNN2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNN2 were set to 33242881 Phenotypes for gene: KCNN2 were set to Intellectual disability; seizures; movement disorder Review for gene: KCNN2 was set to GREEN gene: KCNN2 was marked as current diagnostic