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 (2 variants)
• Congenital myasthenic syndrome 7 (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	45	7	53
missense	1	1	92			94
nonsense			1			1
start loss			2			2
frameshift	1	2	1			4
inframe indel			8			8
splice donor/acceptor (+/-2bp)		2	3			5
splice region			6	13	1	20
non coding				32	19	51
Total	2	5	108	77	26

Variants in SYT2

This is a list of pathogenic ClinVar variants found in the SYT2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-202596616-AGAAAAACAAG-A			Likely benign (Oct 02, 2019)
1-202596619-AAAAC-A			Benign (Jul 26, 2018)
1-202596740-G-A			Benign (Dec 05, 2021)
1-202596763-G-A			Benign (Nov 18, 2023)
1-202596775-G-A			Likely benign (Apr 09, 2022)
1-202596779-G-A			Conflicting classifications of pathogenicity (Oct 01, 2023)
1-202596783-C-T		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
1-202596787-C-G		SYT2-related disorder	Uncertain significance (Dec 02, 2022)
1-202596802-G-C		SYT2-related disorder	Likely benign (Jan 11, 2024)
1-202596820-G-A			Benign (Feb 01, 2024)
1-202596823-G-A			Likely benign (May 13, 2018)
1-202596825-GC-G		Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive	Pathogenic (Aug 06, 2021)
1-202596830-C-T			Uncertain significance (Jan 13, 2022)
1-202596850-G-A			Likely benign (Apr 25, 2023)
1-202596860-C-T			Uncertain significance (Sep 24, 2021)
1-202596874-C-T			Likely benign (Nov 18, 2022)
1-202596875-G-A			Uncertain significance (Jan 18, 2024)
1-202596889-C-T			Likely benign (Oct 19, 2023)
1-202596892-G-A			Likely benign (Nov 08, 2022)
1-202596905-A-T		Congenital myasthenic syndrome 7	Pathogenic (Aug 06, 2021)
1-202596913-G-A			Likely benign (Dec 13, 2023)
1-202596914-T-G		not specified	Uncertain significance (Apr 28, 2022)
1-202596915-T-C			Uncertain significance (Aug 16, 2022)
1-202596920-CCCAGCTTGTCATAGT-C		Congenital myasthenic syndrome 7	Pathogenic (Aug 06, 2021)
1-202596923-A-G		Congenital myasthenic syndrome 7	Pathogenic (Mar 07, 2023)

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