Variant 17-8161461-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014232.3(VAMP2):c.334+12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,613,590 control chromosomes in the GnomAD database, including 44,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3300 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40871 hom. )

Consequence

VAMP2
NM_014232.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.588

Variant links:

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 links:

ENSG00000263620 (HGNC:):

ENSG00000263620 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-8161461-C-G is Benign according to our data. Variant chr17-8161461-C-G is described in ClinVar as [Benign]. Clinvar id is 1321621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAMP2	NM_014232.3 linkuse as main transcript	c.334+12G>C		intron_variant		ENST00000316509.11	NP_055047.2	P63027
VAMP2	NM_001330125.1 linkuse as main transcript	c.340+12G>C		intron_variant			NP_001317054.1	F8WCA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAMP2	ENST00000316509.11 linkuse as main transcript	c.334+12G>C		intron_variant		1	NM_014232.3	ENSP00000314214.6		P63027
ENSG00000263620	ENST00000498285.1 linkuse as main transcript	c.334+12G>C		intron_variant		4		ENSP00000464383.1		L7N2F9

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30535

AN:

152030

Hom.:

3296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.0385

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.191

GnomAD3 exomes

AF:

0.192

AC:

48228

AN:

250746

Hom.:

5254

AF XY:

0.198

AC XY:

26831

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.0430

Gnomad SAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.189

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.231

AC:

337337

AN:

1461442

Hom.:

40871

Cov.:

AF XY:

0.230

AC XY:

167155

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.155

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.0303

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.188

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.201

AC:

30559

AN:

152148

Hom.:

3300

Cov.:

AF XY:

0.196

AC XY:

14582

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.0382

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.226

Hom.:

768

Bravo

AF:

0.199

Asia WGS

AF:

0.110

AC:

382

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2021	- -

Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.5

DANN

Benign

0.53

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over