rs31244

Variant names:

• chr5-76298918-G-A
• rs31244
• NM_014979.4:c.1627G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_014979.4(SV2C):​c.1627G>A​(p.Asp543Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 1,613,424 control chromosomes in the GnomAD database, including 6,155 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (869 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5286 hom.)
• Consequence: SV2C NM_014979.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.22
• Publications: 19 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]

SV2C-AS2 (HGNC:58251):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015901029).
• BP6: Variant 5-76298918-G-A is Benign according to our data. Variant chr5-76298918-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060811.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014979.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	NM_014979.4	MANE Select	c.1627G>A	p.Asp543Asn	missense	Exon 10 of 13	NP_055794.3
	SV2C	NM_001297716.2		c.1627G>A	p.Asp543Asn	missense	Exon 10 of 13	NP_001284645.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	ENST00000502798.7	TSL:1 MANE Select	c.1627G>A	p.Asp543Asn	missense	Exon 10 of 13	ENSP00000423541.2
	SV2C	ENST00000322285.7	TSL:2	c.1627G>A	p.Asp543Asn	missense	Exon 10 of 13	ENSP00000316983.7
	SV2C-AS2	ENST00000502589.2	TSL:5	n.811-12115C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15705 AN: 152090 Hom.: 866 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0951

GnomAD2 exomes AF: 0.0945 AC: 23529 AN: 248978 AF XY: 0.0886

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.0928

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0788

Gnomad OTH exome AF: 0.0873

GnomAD4 exome AF: 0.0813 AC: 118770 AN: 1461216 Hom.: 5286 Cov.: 31 AF XY: 0.0793 AC XY: 57652 AN XY: 726938

African (AFR) AF: 0.139 AC: 4665 AN: 33456

American (AMR) AF: 0.161 AC: 7205 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2958 AN: 26120

East Asian (EAS) AF: 0.0954 AC: 3784 AN: 39682

South Asian (SAS) AF: 0.0332 AC: 2859 AN: 86220

European-Finnish (FIN) AF: 0.111 AC: 5929 AN: 53202

Middle Eastern (MID) AF: 0.0529 AC: 304 AN: 5752

European-Non Finnish (NFE) AF: 0.0776 AC: 86215 AN: 1111718

Other (OTH) AF: 0.0804 AC: 4851 AN: 60368

GnomAD4 genome AF: 0.103 AC: 15718 AN: 152208 Hom.: 869 Cov.: 32 AF XY: 0.106 AC XY: 7896 AN XY: 74408

African (AFR) AF: 0.138 AC: 5743 AN: 41526

American (AMR) AF: 0.141 AC: 2162 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3470

East Asian (EAS) AF: 0.0908 AC: 471 AN: 5188

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4816

European-Finnish (FIN) AF: 0.119 AC: 1261 AN: 10596

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0776 AC: 5278 AN: 68012

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.0862 Hom.: 2845

Bravo AF: 0.107

TwinsUK AF: 0.0844 AC: 313

ALSPAC AF: 0.0869 AC: 335

ESP6500AA AF: 0.139 AC: 528

ESP6500EA AF: 0.0737 AC: 606

ExAC AF: 0.0908 AC: 10970

Asia WGS AF: 0.0700 AC: 243 AN: 3478

EpiCase AF: 0.0747

EpiControl AF: 0.0745

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SV2C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		3.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.071
Sift	Benign	0.27	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.054
MPC		0.15
ClinPred		0.013	T
GERP RS		4.7
Varity_R		0.32
gMVP		0.91
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs31244; hg19: chr5-75594743; COSMIC: COSV107373583; COSMIC: COSV107373583;