dbSNP rs146415005: SV2C:p.Ala102Glu (chr5-76132055-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014979.4(SV2C):c.305C>A(p.Ala102Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. A102G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SV2C
NM_014979.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59

Publications

0 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039466202).

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.305C>A	p.Ala102Glu	missense	Exon 2 of 13	NP_055794.3	Q496J9
	SV2C	NM_001297716.2		c.305C>A	p.Ala102Glu	missense	Exon 2 of 13	NP_001284645.1	B3KT41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	ENST00000502798.7	TSL:1 MANE Select	c.305C>A	p.Ala102Glu	missense	Exon 2 of 13	ENSP00000423541.2	Q496J9
	SV2C	ENST00000322285.7	TSL:2	c.305C>A	p.Ala102Glu	missense	Exon 2 of 13	ENSP00000316983.7	B3KT41

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458956

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25896

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

85804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110342

Other (OTH)

AF:

0.00

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.4

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.022

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.70

M_CAP

Benign

0.0066

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

PhyloP100

1.6

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.62

REVEL

Benign

0.021

Sift

Benign

0.77

Sift4G

Benign

0.77

Polyphen

0.013

Vest4

0.055

MutPred

0.24

Loss of MoRF binding (P = 0.0961)

MVP

0.27

MPC

0.18

ClinPred

0.063

GERP RS

1.9

Varity_R

0.055

gMVP

0.32

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over