rs2358531

Variant names:

• chr5-76183961-G-A
• rs2358531
• NM_014979.4:c.581-10958G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014979.4(SV2C):​c.581-10958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,138 control chromosomes in the GnomAD database, including 48,557 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (48557 hom., cov: 32)
• Consequence: SV2C NM_014979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 10 publications found

Genes affected

SV2C (HGNC:30670): (synaptic vesicle glycoprotein 2C) Predicted to enable transmembrane transporter activity. Predicted to be involved in chemical synaptic transmission; neurotransmitter transport; and transmembrane transport. Predicted to be located in plasma membrane and synaptic vesicle. Predicted to be active in neuron projection and synaptic vesicle membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	NM_014979.4	c.581-10958G>A		intron_variant	Intron 2 of 12	ENST00000502798.7	NP_055794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000502798.7	c.581-10958G>A		intron_variant	Intron 2 of 12	1	NM_014979.4	ENSP00000423541.2
SV2C	ENST00000322285.7	c.581-10958G>A		intron_variant	Intron 2 of 12	2		ENSP00000316983.7

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120712 AN: 152020 Hom.: 48496 Cov.: 32

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.799

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.794 AC: 120832 AN: 152138 Hom.: 48557 Cov.: 32 AF XY: 0.793 AC XY: 58943 AN XY: 74356

African (AFR) AF: 0.904 AC: 37560 AN: 41536

American (AMR) AF: 0.840 AC: 12834 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2851 AN: 3470

East Asian (EAS) AF: 0.914 AC: 4736 AN: 5180

South Asian (SAS) AF: 0.705 AC: 3396 AN: 4816

European-Finnish (FIN) AF: 0.675 AC: 7121 AN: 10556

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49703 AN: 67982

Other (OTH) AF: 0.800 AC: 1690 AN: 2112

Alfa AF: 0.757 Hom.: 190578

Bravo AF: 0.815

Asia WGS AF: 0.822 AC: 2860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs2358531; hg19: chr5-75479786;