rs2308169

Positions:

• chr3-12045602-ACTATG-A
• chr3-12045602-ACTATG-ACTATGCTATG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_133625.6(SYN2):​c.377+40677_377+40681delATGCT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (33498 hom., cov: 0)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN2	NM_133625.6	c.377+40677_377+40681delATGCT		intron_variant		ENST00000621198.5	NP_598328.1
SYN2	NM_003178.6	c.377+40677_377+40681delATGCT		intron_variant			NP_003169.2
SYN2	XM_006713311.4	c.377+40677_377+40681delATGCT		intron_variant			XP_006713374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.377+40677_377+40681delATGCT		intron_variant		1	NM_133625.6	ENSP00000480050.1
SYN2	ENST00000620175.4	c.377+40677_377+40681delATGCT		intron_variant		1		ENSP00000484916.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 96850 AN: 151314 Hom.: 33484 Cov.: 0

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.640 AC: 96885 AN: 151432 Hom.: 33498 Cov.: 0 AF XY: 0.645 AC XY: 47735 AN XY: 73960

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.699

Alfa AF: 0.686 Hom.: 4574

Bravo AF: 0.626

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2308169; hg19: chr3-12087102;