Variant 17-8162290-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM1BP4_StrongBP6_ModerateBS2

The NM_014232.3(VAMP2):c.82A>G(p.Ser28Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000561 in 1,579,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

VAMP2
NM_014232.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.56

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM1

In a mutagenesis_site Significant loss of phosphorylation; when associated with A-61, A-75 and A-80. (size 0) in uniprot entity VAMP2_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.023501813).

BP6

Variant 17-8162290-T-C is Benign according to our data. Variant chr17-8162290-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3257649.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAMP2	NM_014232.3 linkuse as main transcript	c.82A>G	p.Ser28Gly	missense_variant	2/5	ENST00000316509.11	NP_055047.2	P63027
VAMP2	NM_001330125.1 linkuse as main transcript	c.88A>G	p.Ser30Gly	missense_variant	2/5		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.82A>G	p.Ser28Gly	missense_variant	2/5	1	NM_014232.3	ENSP00000314214.6		P63027
ENSG00000263620	ENST00000498285.1 linkuse as main transcript	c.82A>G	p.Ser28Gly	missense_variant	2/5	4		ENSP00000464383.1		L7N2F9

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000627

AC:

137

AN:

218650

Hom.:

AF XY:

0.000678

AC XY:

AN XY:

119480

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000201

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000979

Gnomad NFE exome

AF:

0.000868

Gnomad OTH exome

AF:

0.000769

GnomAD4 exome

AF:

0.000572

AC:

817

AN:

1427606

Hom.:

Cov.:

AF XY:

0.000576

AC XY:

409

AN XY:

709606

show subpopulations

Gnomad4 AFR exome

AF:

0.000160

Gnomad4 AMR exome

AF:

0.000145

Gnomad4 ASJ exome

AF:

0.00252

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000486

Gnomad4 FIN exome

AF:

0.00142

Gnomad4 NFE exome

AF:

0.000561

Gnomad4 OTH exome

AF:

0.000833

GnomAD4 genome

AF:

0.000460

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000731

Hom.:

Bravo

AF:

0.000442

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000774

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

VAMP2: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Uncertain

0.57

.;D;.;.

Eigen

Benign

-0.066

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;M;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.1

.;D;D;.

REVEL

Benign

0.087

Sift

Benign

0.040

.;D;D;.

Sift4G

Benign

0.20

.;.;T;.

Polyphen

0.060

.;B;.;.

Vest4

0.13, 0.13, 0.14

MVP

0.21

MPC

0.097

ClinPred

0.068

GERP RS

4.6

Varity_R

0.56

gMVP

0.84

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