SYT2

synaptotagmin 2, the group of Synaptotagmins

Basic information

Region (hg38): 1:202590596-202710454

Links

ENSG00000143858

∙ NCBI:127833 ∙ OMIM:600104 ∙ HGNC:11510 ∙ Uniprot:Q8N9I0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

congenital myasthenic syndrome 7 (Strong), mode of inheritance: AD
congenital myasthenic syndrome 7 (Strong), mode of inheritance: AD
congenital myasthenic syndrome 7 (Strong), mode of inheritance: AR
congenital myasthenic syndrome 7 (Moderate), mode of inheritance: AD
presynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AD
congenital myasthenic syndrome 7 (Strong), mode of inheritance: AD
congenital myasthenic syndrome 7 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital 7A, presynaptic, and distal motor neuropathy, autosomal dominant; Myasthenic syndrome, congenital 7B, presynaptic, autosomal recessive	AD/AR	Musculoskeletal; Neurologic	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	25192047; 26519543; 32250532; 32776697; 33659639; 34037996

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SYT2 gene.

not_provided (239 variants)
Inborn_genetic_diseases (40 variants)
Congenital_myasthenic_syndrome_7 (14 variants)
SYT2-related_disorder (9 variants)
not_specified (8 variants)
Myasthenic_syndrome,_congenital,_7B,_presynaptic,_autosomal_recessive (7 variants)
Respiratory_distress (1 variants)
SYT2-related_myasthenia (1 variants)
Peripheral_axonal_neuropathy (1 variants)
Muscle_weakness (1 variants)
Flexion_contracture (1 variants)
Congenital_myasthenic_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000177402.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				52 clinvar	6 clinvar	58
missense	3 clinvar	4 clinvar	125 clinvar	2 clinvar		134
nonsense	1 clinvar		1 clinvar			2
start loss			2			2
frameshift	3 clinvar	4 clinvar	1 clinvar			8
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	3 clinvar			7
Total	8	11	132	54	6

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SYT2	protein_coding	protein_coding	ENST00000367267	8	119822

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.981	0.0187	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.98	159	246	0.645	0.0000135	2788
Missense in Polyphen		42	81.221	0.51711		950
Synonymous	0.887	91	102	0.888	0.00000643	788
Loss of Function	3.54	1	16.6	0.0604	6.99e-7	223

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties (By similarity). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:P46097, ECO:0000269|PubMed:23999003}.;
Disease: DISEASE: Myasthenic syndrome, congenital, 7, presynaptic (CMS7) [MIM:616040]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS7 is an autosomal dominant, presynaptic disorder resembling Lambert-Eaton myasthenic syndrome. Affected individuals have a variable degree of proximal and distal limb weakness, muscle fatigue that improves with rest, mild gait difficulties, and reduced or absent deep tendon reflexes. {ECO:0000269|PubMed:25192047}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Disease;Vesicle-mediated transport;Membrane Trafficking;Uptake and actions of bacterial toxins;Neurotoxicity of clostridium toxins;Infectious disease;Neuronal System;Clathrin-mediated endocytosis;Toxicity of botulinum toxin type B (BoNT/B);Neurexins and neuroligins;Cargo recognition for clathrin-mediated endocytosis;Protein-protein interactions at synapses (Consensus)

Recessive Scores

pRec: 0.246

Intolerance Scores

loftool: 0.225
rvis_EVS: -0.63
rvis_percentile_EVS: 17.03

Haploinsufficiency Scores

pHI: 0.276
hipred: Y
hipred_score: 0.768
ghis: 0.680

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.792

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Syt2
Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype;

Zebrafish Information Network

Gene name: syt2b
Affected structure: motor neuron
Phenotype tag: abnormal
Phenotype quality: physical object quality

Gene ontology

Biological process: regulation of dopamine secretion;synaptic vesicle exocytosis;vesicle-mediated transport;calcium ion regulated exocytosis;regulation of calcium ion-dependent exocytosis;synaptic vesicle endocytosis;calcium ion-regulated exocytosis of neurotransmitter;membrane organization;cellular response to calcium ion;positive regulation of dendrite extension
Cellular component: plasma membrane;integral component of membrane;cell junction;axon;clathrin-coated vesicle membrane;synaptic vesicle membrane;dense core granule;chromaffin granule membrane;exocytic vesicle
Molecular function: SNARE binding;phosphatidylserine binding;calcium ion binding;protein binding;calcium-dependent phospholipid binding;syntaxin binding;clathrin binding;inositol 1,3,4,5 tetrakisphosphate binding