Genetic Variant SYN2:c.684+2633A>G (chr3-12148468-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_133625.6(SYN2):c.684+2633A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,338 control chromosomes in the GnomAD database, including 2,906 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 0.16 ( 2899 hom., cov: 32)

Exomes 𝑓: 0.27 ( 7 hom. )

Consequence

SYN2
NM_133625.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.196

Publications

25 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:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN2	NM_133625.6 link	c.684+2633A>G		intron_variant	Intron 4 of 12	ENST00000621198.5	NP_598328.1	Q92777-1Q86VA8B3KRB3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYN2	ENST00000621198.5 link	c.684+2633A>G	intron_variant	Intron 4 of 12	1	NM_133625.6	ENSP00000480050.1	Q92777-1
SYN2	ENST00000620175.4 link	c.684+2633A>G	intron_variant	Intron 4 of 10	1		ENSP00000484916.1	Q92777-2
SYN2	ENST00000424884.1 link	n.433+2633A>G	intron_variant	Intron 4 of 4	4
SYN2	ENST00000439861.5 link	n.-89A>G	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23862

AN:

152096

Hom.:

2897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0442

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.0998

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.142

GnomAD4 exome

AF:

0.274

AC:

AN:

124

Hom.:

AF XY:

0.255

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.100

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.600

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.357

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.200

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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

AF:

0.157

AC:

23860

AN:

152214

Hom.:

2899

Cov.:

AF XY:

0.168

AC XY:

12478

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0441

AC:

1834

AN:

41560

American (AMR)

AF:

0.211

AC:

3224

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0998

AC:

346

AN:

3468

East Asian (EAS)

AF:

0.563

AC:

2912

AN:

5168

South Asian (SAS)

AF:

0.431

AC:

2079

AN:

4822

European-Finnish (FIN)

AF:

0.235

AC:

2490

AN:

10592

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10568

AN:

67998

Other (OTH)

AF:

0.146

AC:

308

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

952

1905

2857

3810

4762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.165

Hom.:

1450

Bravo

AF:

0.144

Asia WGS

AF:

0.436

AC:

1515

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.2

(source)

DANN

Benign

0.64

PhyloP100

0.20

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

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