SV2A

protein-coding

synaptic vesicle glycoprotein 2A, the group of Solute carrier family 22

Gene summary

The protein encoded by this gene is one of three related synaptic vesicle proteins. The encoded protein may interact with synaptotagmin to enhance low frequency neurotransmission in quiescent neurons. [provided by RefSeq, Jun 2016]

MANE transcript

NM_014849.5

Inheritance

SD, AR, AD

ClinVar variants

P:3U:84B:22

Top phenotype

Developmental and epileptic encephalopathy 113

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr1:149,903,318-149,917,844

External References & Databases

Ensembl (ENSG00000159164)

Transcript & Mutation Effects

hg38 • Region Span ~14.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy 113MODERATE

Inheritance Pattern: SD

Disease ID:MONDO:0958330

Submitter: PanelApp Australia

developmental and epileptic encephalopathy 113LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0958330

Submitter: Ambry Genetics

epilepsyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005027

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 113AR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 26002053; 37985816

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SV2A variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 80

not providedTotal: 21

Developmental and epileptic encephalopathy 113Total: 4

Neurodevelopmental disorderTotal: 1

Inborn genetic diseasesTotal: 1

See casesTotal: 1

SV2A-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014849.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	15 clinvar	5 clinvar	24
missense			78 clinvar	2 clinvar		80
nonsense	1 clinvar	2 clinvar				3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	2	84	17	5	109

Highest pathogenic variant AF is 0.0000061566498

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014849.5	RefSeq	NP_055664.3	12	MANE Select
ENST00000369146.8	Ensembl	ENSP00000358142.3	12	MANE Select
NM_001278719.2	RefSeq	NP_001265648.1	3	Standard
NM_001328674.2	RefSeq	NP_001315603.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

ECM-receptor interaction - Homo sapiens (human)
Disease
Toxicity of botulinum toxin type A (BoNT/A)
Toxicity of botulinum toxin type D (BoNT/D)
Toxicity of botulinum toxin type F (BoNT/F)

Biological Process

cellular calcium ion homeostasis
regulation of gamma-aminobutyric acid secretion
synaptic vesicle priming
transmembrane transport

Molecular Function

protein kinase binding
transmembrane transporter activity

Cellular Component

endoplasmic reticulum
plasma membrane
cell-cell junction
synaptic vesicle
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369146
Coding exons: 12
Length: 14565
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.12	328	455	0.721	0.0000285	4853
Missense (PolyPhen)		84	198.11	0.42401		2202
Synonymous	0.200	185	189	0.981	0.0000123	1501
Loss of Function	4.36	9	38.0	0.237	0.00000246	366

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000070	0.000070	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.345

Intolerance Scores

LoFtool: 0.393
RVIS EVS: -1.24
RVIS percentile EVS: 5.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.126

Gene Damage Prediction

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