Variant 15-91252421-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001323032.3(SV2B):c.685C>T(p.Arg229Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000504 in 1,613,330 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

SV2B
NM_001323032.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

Variant links:

Genes affected

SV2B (HGNC:16874): (synaptic vesicle glycoprotein 2B) This gene encodes a member of the synaptic vesicle proteins 2 (SV2) family and major facilitator superfamily of proteins. This protein and other members of the family are localized to synaptic vesicles and may function in the regulation of vesicle trafficking and exocytosis. Studies in mice suggest that the encoded protein may act as a protein receptor for botulinum neurotoxin E in neurons, and that this protein may be important for the integrity of the glomerular filtration barrier. This gene shows reduced expression in areas of synaptic loss in the hippocampus of human temporal lobe epilepsy patients. [provided by RefSeq, Sep 2016]

SV2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SV2B	NM_001323032.3 linkuse as main transcript	c.685C>T	p.Arg229Trp	missense_variant	4/13	ENST00000394232.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SV2B	ENST00000394232.6 linkuse as main transcript	c.685C>T	p.Arg229Trp	missense_variant	4/13	5	NM_001323032.3	P1	Q7L1I2-1
SV2B	ENST00000330276.4 linkuse as main transcript	c.685C>T	p.Arg229Trp	missense_variant	3/12	1		P1	Q7L1I2-1
SV2B	ENST00000557410.5 linkuse as main transcript	c.685C>T	p.Arg229Trp	missense_variant, NMD_transcript_variant	5/15	1			Q7L1I2-1
SV2B	ENST00000545111.6 linkuse as main transcript	c.232C>T	p.Arg78Trp	missense_variant	3/12	2			Q7L1I2-2

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000236

AC:

AN:

250502

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000415

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000517

AC:

756

AN:

1461230

Hom.:

Cov.:

AF XY:

0.000509

AC XY:

370

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000649

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000375

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.000355

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000713

EpiControl

AF:

0.000298

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2022

The c.685C>T (p.R229W) alteration is located in exon 5 (coding exon 3) of the SV2B gene. This alteration results from a C to T substitution at nucleotide position 685, causing the arginine (R) at amino acid position 229 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.72

.;D;D

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;.;D

M_CAP

Benign

0.056

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Uncertain

0.32

MutationAssessor

Pathogenic

2.9

.;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.63

MVP

0.59

MPC

0.97

ClinPred

0.51

GERP RS

5.4

Varity_R

0.82

gMVP

0.70

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