SYT2

Chr 1ADAR

synaptotagmin 2

Also known as: CMS7, CMS7A, CMS7B, MYSPC, SytII

NCBI Gene: 127833ENSG00000143858UniProt: Q8N9I0

This gene encodes a synaptic vesicle membrane protein. The encoded protein is thought to function as a calcium sensor in vesicular trafficking and exocytosis. Mutations in this gene are associated with myasthenic syndrome, presynaptic, congenital, with or without motor neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

Primary Disease Associations & Inheritance

Myasthenic syndrome, congenital, 7A, presynaptic, and distal motor neuropathy, autosomal dominantMIM #616040
AD
Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessiveMIM #619461
AR
0
Active trials
0
Pathogenic / LP
0
ClinVar variants
9
Pubs (1 yr)
2.0
Missense Z
0.29
LOEUF· LoF intolerant
Clinical Summary— SYT2
🧬
Gene-Disease Validity (ClinGen)
congenital myasthenic syndrome 7 · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.981
Z-score 3.54
OE 0.06 (0.02–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.98Z-score
OE missense 0.65 (0.57–0.74)
159 obs / 246.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.06 (0.02–0.29)
0≤0.351.4
Missense OE0.65 (0.57–0.74)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 1 / 16.6Missense obs/exp: 159 / 246.4Syn Z: 0.89
LOFDN
DN
0.5869th %ile
GOF
0.5856th %ile
LOF
0.62top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.29
DN1 literature citation

Literature Evidence

DNValidation of this new variant was accomplished by characterization of the mutation homologous to the human c. 1112T>A variant in Drosophila, confirming its dominant-negative effect on neurotransmitter release.PMID:30533528

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

SYT2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SYT2-related congenital onset presynaptic myasthenic syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
frameshift variantstop gainedwhole partial gene deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients