Genetic Variant SYN2:c.*413C>G (chr3-12183853-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000620175.4(SYN2):c.*413C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,025,818 control chromosomes in the GnomAD database, including 1,908 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 0.085 ( 1005 hom., cov: 32)

Exomes 𝑓: 0.036 ( 903 hom. )

Consequence

SYN2
ENST00000620175.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.363

Publications

7 publications found

Variant links:

Genes affected

SYN2 (HGNC:11495): (synapsin II) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family encodes a neuron-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal. Polymorphisms in this gene are associated with abnormal presynaptic function and related neuronal disorders, including autism, epilepsy, bipolar disorder and schizophrenia. Alternative splicing of this gene results in multiple transcript variants. The tissue inhibitor of metalloproteinase 4 gene is located within an intron of this gene and is transcribed in the opposite direction. [provided by RefSeq, Feb 2014]

SYN2 links:

ENSG00000288952 (HGNC:):

ENSG00000288952 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN2	NM_133625.6 link	c.1369+481C>G		intron_variant	Intron 11 of 12	ENST00000621198.5	NP_598328.1	Q92777-1Q86VA8B3KRB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5 link	c.1369+481C>G		intron_variant	Intron 11 of 12	1	NM_133625.6	ENSP00000480050.1		Q92777-1

Frequencies

GnomAD3 genomes

AF:

0.0852

AC:

12954

AN:

152002

Hom.:

1004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0436

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.0368

Gnomad FIN

AF:

0.0256

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0349

Gnomad OTH

AF:

0.0757

GnomAD4 exome

AF:

0.0356

AC:

31111

AN:

873698

Hom.:

903

Cov.:

AF XY:

0.0348

AC XY:

14134

AN XY:

405842

show subpopulations

African (AFR)

AF:

0.213

AC:

3417

AN:

16008

American (AMR)

AF:

0.0246

AC:

AN:

1668

Ashkenazi Jewish (ASJ)

AF:

0.0381

AC:

232

AN:

6096

East Asian (EAS)

AF:

0.187

AC:

734

AN:

3926

South Asian (SAS)

AF:

0.0259

AC:

576

AN:

22282

European-Finnish (FIN)

AF:

0.0272

AC:

AN:

2976

Middle Eastern (MID)

AF:

0.0397

AC:

AN:

1790

European-Non Finnish (NFE)

AF:

0.0311

AC:

24557

AN:

789200

Other (OTH)

AF:

0.0471

AC:

1402

AN:

29752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1744

3488

5232

6976

8720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1324

2648

3972

5296

6620

<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

AF:

0.0852

AC:

12955

AN:

152120

Hom.:

1005

Cov.:

AF XY:

0.0830

AC XY:

6170

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.197

AC:

8171

AN:

41472

American (AMR)

AF:

0.0435

AC:

665

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0377

AC:

131

AN:

3472

East Asian (EAS)

AF:

0.193

AC:

996

AN:

5172

South Asian (SAS)

AF:

0.0362

AC:

174

AN:

4810

European-Finnish (FIN)

AF:

0.0256

AC:

271

AN:

10598

Middle Eastern (MID)

AF:

0.0240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0349

AC:

2371

AN:

68000

Other (OTH)

AF:

0.0749

AC:

158

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

545

1090

1634

2179

2724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0176

Hom.:

Bravo

AF:

0.0945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.58

(source)

DANN

Benign

0.55

PhyloP100

0.36

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over