Intellectual disability
Gene: KIF2A

KIF2A (kinesin family member 2A)
EnsemblGeneIds (GRCh38): ENSG00000068796
EnsemblGeneIds (GRCh37): ENSG00000068796
OMIM: 602591, Gene2Phenotype
KIF2A is in 5 panels

6 reviews

Catherine Snow (Genomics England)

Three further cases identified in the literature.
PMID:27747449 (Cavallin et al 2017) detected two de novo p.Ser317Asn and p.His321Pro mutations in KIF2A in two patients with lissencephaly and microcephaly. Case 1 had DD, no epilepsy but was only 9 months old at last reporting. Case 2 had neonatal seizures and severe DD.
PMID:27896282 (Tian et al 2016) report a patient with lissencephaly, developmental delay, and infantile spasms, due to de novo heterozygous variant in KIF2A (p.Thr320Ile).
Most cases identified have epilepsy first however as one individual did not have seizures KIF2A is relevant for the ID panel.
Therefore upgrading rating from Amber to Green as now sufficient (>3) unrelated cases.
Created: 24 Jul 2019, 10:38 a.m. | Last Modified: 25 Jul 2019, 8:29 a.m.

Panel Version: 2.977

Created: 24 Jul 2019, 10:38 a.m.
Last Modified: 25 Jul 2019, 8:29 a.m.
Panel version: 2.974

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Further to the articles that have been cited previously, 3 additional individuals with KIF2A de novo variants and a similar phenotype have been reported:

PMID 27747449 reports on a 9 month-old female with congenital microcephaly and posteriorly predominant lissencephaly, with a de novo missense variant (p.Ser317Asn) in KIF2A. A second patient with lissencephaly of the same type and severe ID is described. This individual was found to have a de novo missense variant in KIF2A (p.His321Pro). The authors have excluded alternative causes (gene panel analysis and prior aCGH performed for both patients). p.Ser317 and p.His321 are proposed as hotspots since the first variant (Ser317Asn) was previously described, while His321Pro concerns the same AA as in a previously described individual (His321Asp) [both in PMID 23603762].

PMID 27896282 reports on a 9 month-old female with lissencephaly and a de novo missense variant p.Thr320Ile. Expression studies were suggestive of a different pattern of cellular localization compared to wt and of abnormal microtubules.

This variant has also been submitted as likely pathogenic in ClinVar by a (seemingly) different submitter (Variation 435642).

[The variants in the different articles would correspond to the same AA positions whether NM_004520 or NM_001098511 is used as a reference sequence].
Created: 13 Aug 2018, 12:23 p.m.

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

Phenotypes
MALFORMATIONS OF CORTICAL DEVELOPMENT AND MICROCEPHALY

Publications

Created: 13 Aug 2018, 12:23 p.m.

Panel version: 2.362

Olivia Niblock (Genomics England Curator)

I don't know

Amber - two reports of different variants in this gene linked to severe developmental delay, amongst other phenotypes (PMID:23603762). There is a 5q12 deletion reported in the literature which encompasses this gene and eleven others - patients have been noted to express mental retardation(PMID:21594994)
Created: 13 Dec 2017, 10:16 p.m.

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

Publications

Created: 13 Dec 2017, 10:16 p.m.

Panel version: Imported from Intellectual disability update Dec 2017 panel version 0.5

Caroline Wright (Sanger)

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
MALFORMATIONS OF CORTICAL DEVELOPMENT AND MICROCEPHALY.

Publications

23603762

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Lu Raymond (university of cambridge )

I don't know

Created: 23 Feb 2016, 10:17 a.m.

Panel version: 0.306

Richard Scott (Genomics England Curator)

Comment on list classification: 2 cases reported to date. Pending further data before diagnostic
Created: 7 Feb 2016, 9:35 p.m.

Created: 7 Feb 2016, 9:35 p.m.

Panel version: 0.166

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green

Phenotypes

Cortical dysplasia, complex, with other brain malformations 3, 615411

OMIM

602591

Clinvar variants

Variants in KIF2A

Penetrance

Complete

Publications

Panels with this gene