17-8159265-A-G

Variant names:

• chr17-8159265-A-G
• rs1150
• NM_014232.3:c.*1590T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014232.3(VAMP2):​c.*1590T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,260 control chromosomes in the GnomAD database, including 34,117 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (34105 hom., cov: 27)
  • Exomes 𝑓: 0.79 (12 hom.)
• Consequence: VAMP2 NM_014232.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 24 publications found

Genes affected

VAMP2 (HGNC:12643): (vesicle associated membrane protein 2) The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. This gene is thought to participate in neurotransmitter release at a step between docking and fusion. The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and synaptotagmin. It also forms a distinct complex with synaptophysin. It is a likely candidate gene for familial infantile myasthenia (FIMG) because of its map location and because it encodes a synaptic vesicle protein of the type that has been implicated in the pathogenesis of FIMG. [provided by RefSeq, Jul 2008]

VAMP2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000263620 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014232.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP2	NM_014232.3	MANE Select	c.*1590T>C		3_prime_UTR	Exon 5 of 5	NP_055047.2	P63027
	VAMP2	NM_001330125.1		c.*1590T>C		3_prime_UTR	Exon 5 of 5	NP_001317054.1	F8WCA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP2	ENST00000316509.11	TSL:1 MANE Select	c.*1590T>C		3_prime_UTR	Exon 5 of 5	ENSP00000314214.6	P63027
	ENSG00000263620	ENST00000498285.1	TSL:4	c.334+2208T>C		intron	N/A	ENSP00000464383.1	L7N2F9

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101124 AN: 151100 Hom.: 34080 Cov.: 27

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.786 AC: 33 AN: 42 Hom.: 12 Cov.: 0 AF XY: 0.778 AC XY: 28 AN XY: 36

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.765 AC: 26 AN: 34

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.875 AC: 7 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.669 AC: 101194 AN: 151218 Hom.: 34105 Cov.: 27 AF XY: 0.675 AC XY: 49800 AN XY: 73820

African (AFR) AF: 0.645 AC: 26515 AN: 41114

American (AMR) AF: 0.698 AC: 10594 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1703 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2547 AN: 5128

South Asian (SAS) AF: 0.729 AC: 3493 AN: 4792

European-Finnish (FIN) AF: 0.780 AC: 8153 AN: 10450

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.680 AC: 46092 AN: 67792

Other (OTH) AF: 0.649 AC: 1358 AN: 2092

Alfa AF: 0.666 Hom.: 48475

Bravo AF: 0.658

Asia WGS AF: 0.626 AC: 2177 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1150; hg19: chr17-8062583;