chr15-91252421-C-T

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

5
11
3

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]

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
SV2BNM_001323032.3 linkuse as main transcriptc.685C>T p.Arg229Trp missense_variant 4/13 ENST00000394232.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SV2BENST00000394232.6 linkuse as main transcriptc.685C>T p.Arg229Trp missense_variant 4/135 NM_001323032.3 P1Q7L1I2-1
SV2BENST00000330276.4 linkuse as main transcriptc.685C>T p.Arg229Trp missense_variant 3/121 P1Q7L1I2-1
SV2BENST00000557410.5 linkuse as main transcriptc.685C>T p.Arg229Trp missense_variant, NMD_transcript_variant 5/151 Q7L1I2-1
SV2BENST00000545111.6 linkuse as main transcriptc.232C>T p.Arg78Trp missense_variant 3/122 Q7L1I2-2

Frequencies

GnomAD3 genomes
AF:
0.000375
AC:
57
AN:
152100
Hom.:
0
Cov.:
32
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:
59
AN:
250502
Hom.:
0
AF XY:
0.000214
AC XY:
29
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.:
0
Cov.:
30
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:
57
AN:
152100
Hom.:
0
Cov.:
32
AF XY:
0.000269
AC XY:
20
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.:
0
Bravo
AF:
0.000355
TwinsUK
AF:
0.00135
AC:
5
ALSPAC
AF:
0.00156
AC:
6
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000814
AC:
7
ExAC
AF:
0.000189
AC:
23
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 submitterclinical testingAmbry GeneticsMay 06, 2022The 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
T
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.72
.;D;D
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.98
D;.;D
M_CAP
Benign
0.056
D
MetaRNN
Uncertain
0.51
D;D;D
MetaSVM
Uncertain
0.32
D
MutationAssessor
Pathogenic
2.9
.;M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.73
T
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
D
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.

Other links and lift over

dbSNP: rs148980578; hg19: chr15-91795651; COSMIC: COSV57698566; COSMIC: COSV57698566; API