Variant chr15-91252418-T-A 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.682T>A(p.Ser228Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SV2B
NM_001323032.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

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:

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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	Protein	UniProt
SV2B	NM_001323032.3 linkuse as main transcript	c.682T>A	p.Ser228Thr	missense_variant	4/13	ENST00000394232.6	NP_001309961.1	Q7L1I2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SV2B	ENST00000394232.6 linkuse as main transcript	c.682T>A	p.Ser228Thr	missense_variant	4/13	5	NM_001323032.3	ENSP00000377779.1	Q7L1I2-1
SV2B	ENST00000330276.4 linkuse as main transcript	c.682T>A	p.Ser228Thr	missense_variant	3/12	1		ENSP00000332818.4	Q7L1I2-1
SV2B	ENST00000557410.5 linkuse as main transcript	n.682T>A		non_coding_transcript_exon_variant	5/15	1		ENSP00000450992.1	Q7L1I2-1
SV2B	ENST00000545111.6 linkuse as main transcript	c.229T>A	p.Ser77Thr	missense_variant	3/12	2		ENSP00000443243.2	Q7L1I2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461424

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 10, 2024

The c.682T>A (p.S228T) alteration is located in exon 5 (coding exon 3) of the SV2B gene. This alteration results from a T to A substitution at nucleotide position 682, causing the serine (S) at amino acid position 228 to be replaced by a threonine (T). 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

Benign

0.18

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.93

D;.;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.5

.;L;L

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.62

N;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.014

D;D;D

Sift4G

Benign

0.18

T;T;T

Polyphen

0.87

.;P;P

Vest4

0.56

MutPred

0.52

.;Loss of disorder (P = 0.0573);Loss of disorder (P = 0.0573);

MVP

0.51

MPC

0.48

ClinPred

0.87

GERP RS

5.4

Varity_R

0.22

gMVP

0.56

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over