15-91284050-C-G

Variant names:

• chr15-91284050-C-G
• rs193920952
• NM_001323032.3:c.1537C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014848.7(SV2B):​c.1537C>G​(p.Arg513Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R513W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SV2B NM_014848.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014848.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2B	NM_001323032.3	MANE Select	c.1537C>G	p.Arg513Gly	missense	Exon 11 of 13	NP_001309961.1
	SV2B	NM_001323031.2		c.1537C>G	p.Arg513Gly	missense	Exon 11 of 13	NP_001309960.1
	SV2B	NM_001323037.3		c.1537C>G	p.Arg513Gly	missense	Exon 12 of 14	NP_001309966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2B	ENST00000394232.6	TSL:5 MANE Select	c.1537C>G	p.Arg513Gly	missense	Exon 11 of 13	ENSP00000377779.1
	SV2B	ENST00000330276.4	TSL:1	c.1537C>G	p.Arg513Gly	missense	Exon 10 of 12	ENSP00000332818.4
	SV2B	ENST00000557410.5	TSL:1	n.1537C>G		non_coding_transcript_exon	Exon 12 of 15	ENSP00000450992.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.024
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0057	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.1
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.19
Sift	Benign	0.070	T
Sift4G	Benign	0.32	T
Polyphen		0.31	B
Vest4		0.42
MutPred		0.73		Loss of helix (P = 0.028)
MVP		0.27
MPC		0.67
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.19
gMVP		0.78
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs193920952; hg19: chr15-91827280;