Ataxia and cerebellar anomalies - narrow panel

Gene: SNAPIN

Green List (high evidence)

Comment on list classification: Cerebellar hypoplasia/atrophy was reported in three unrelated foetuses and three other unrelated patients. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 2 Jan 2026, 7:37 p.m. | Last Modified: 2 Jan 2026, 7:37 p.m.

Panel Version: 8.45

PMID:26539891 (2015) reported whole exome sequencing of 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. One of these patients was identified with homozygous variant in SNAPIN gene (c.163C>T/ p.Arg55Trp). The patient displayed intellectual disability, microcephaly, cortical atrophy, bulbar and cerebellar hypoplasia, sensorineural polyneuropathy and hypotonia.

PMID:40930097 (2025) reported six patients from five unrelated families presenting with neuroanatomical, craniofacial, and skeletal anomalies and were identified with homozygous variants in SNAPIN gene. This included four foetuses from three unrelated families (had nonsense or splice site variants - c.91G>T/ p.Glu31Ter, c.144−1G>A & c.112C>T/ p.Gln38Ter) and two unrelated patients aged eight years old and one year old (had missense variants - c.147G>C/ p.Glu49Asp & c.163C>T/ p.Arg55Trp). One of the foetuses had intrauterine demise at 26 weeks' gestation, and the other 3 pregnancies ended in termination. Brain abnormalities in the patients included ventriculomegaly (5/6), cerebellar hypoplasia/ atrophy (5/6) and corpus callosum agenesis (4/6). The other phenotypes included clubfeet (4/6), flexion contractures (4/6), microcephaly (3/6) and micrognathia/retrognathia (4/6).

Functional evidence is also available from zebrafish gene ablation models, which recapitulated human-relevant disease phenotypes.

This gene has been associated with relevant phenotype in OMIM (MIM #621393, last accessed on 02 January 2026), but not yet in Gene2Phenotype or ClinGen.
Sources: Literature

Created: 2 Jan 2026, 7:33 p.m. | Last Modified: 2 Jan 2026, 7:51 p.m.

Panel Version: 8.45

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, OMIM:621393

Publications

• 26539891
• 40930097