chr15-91252421-C-T
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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
NM_001323032.3 missense
Scores
5
11
3
Clinical Significance
Conservation
PhyloP100: 3.64
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]
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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 | UniProt |
---|---|---|---|---|---|---|---|
SV2B | NM_001323032.3 | 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 | c.685C>T | p.Arg229Trp | missense_variant | 4/13 | 5 | NM_001323032.3 | P1 | |
SV2B | ENST00000330276.4 | c.685C>T | p.Arg229Trp | missense_variant | 3/12 | 1 | P1 | ||
SV2B | ENST00000557410.5 | c.685C>T | p.Arg229Trp | missense_variant, NMD_transcript_variant | 5/15 | 1 | |||
SV2B | ENST00000545111.6 | c.232C>T | p.Arg78Trp | missense_variant | 3/12 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000375 AC: 57AN: 152100Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000236 AC: 59AN: 250502Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135370
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GnomAD4 exome AF: 0.000517 AC: 756AN: 1461230Hom.: 0 Cov.: 30 AF XY: 0.000509 AC XY: 370AN XY: 726896
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GnomAD4 genome AF: 0.000375 AC: 57AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74286
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
.;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;D
Vest4
MVP
MPC
0.97
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at