Variant chr15-91226295-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001323032.3(SV2B):c.32G>C(p.Gly11Ala) 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 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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: 1.97

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051172405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SV2B	NM_001323032.3 linkuse as main transcript	c.32G>C	p.Gly11Ala	missense_variant	2/13	ENST00000394232.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SV2B	ENST00000394232.6 linkuse as main transcript	c.32G>C	p.Gly11Ala	missense_variant	2/13	5	NM_001323032.3	P1	Q7L1I2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727216

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:

8.99e-7

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

May 16, 2024

The c.32G>C (p.G11A) alteration is located in exon 3 (coding exon 1) of the SV2B gene. This alteration results from a G to C substitution at nucleotide position 32, causing the glycine (G) at amino acid position 11 to be replaced by an alanine (A). 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

0.088

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.9

DANN

Benign

0.79

DEOGEN2

Benign

0.070

T;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.060

Sift

Benign

0.59

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.020

B;B

Vest4

0.13

MutPred

0.17

Gain of catalytic residue at G11 (P = 0.0232);Gain of catalytic residue at G11 (P = 0.0232);

MVP

0.12

MPC

0.32

ClinPred

0.073

GERP RS

2.2

Varity_R

0.048

gMVP

0.25

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