rs2307973

Variant names:

• chr3-12188015-TTC-T
• rs2307973
• NM_133625.6:c.1613+405_1613+406delCT

Your query was ambiguous. Multiple possible variants found:

• chr3-12188015-TTC-T
• chr3-12188015-TTC-TTCTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_133625.6(SYN2):​c.1613+405_1613+406delCT 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 0.73 (36795 hom., cov: 0)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614
• Publications: 2 publications found

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]

ENSG00000288952 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN2	NM_133625.6	c.1613+405_1613+406delCT		intron_variant	Intron 12 of 12	ENST00000621198.5	NP_598328.1
SYN2	XM_006713312.5	c.1130+405_1130+406delCT		intron_variant	Intron 9 of 9		XP_006713375.1
SYN2	XM_017007087.2	c.941+405_941+406delCT		intron_variant	Intron 8 of 8		XP_016862576.1
SYN2	XM_006713313.3	c.842+405_842+406delCT		intron_variant	Intron 9 of 9		XP_006713376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.1613+404_1613+405delTC		intron_variant	Intron 12 of 12	1	NM_133625.6	ENSP00000480050.1
SYN2	ENST00000439861.5	n.1232+404_1232+405delTC		intron_variant	Intron 9 of 9	2
ENSG00000288952	ENST00000690965.2	n.527+4351_527+4352delGA		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.726 AC: 104166 AN: 143558 Hom.: 36762 Cov.: 0

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.726 AC: 104248 AN: 143676 Hom.: 36795 Cov.: 0 AF XY: 0.729 AC XY: 51229 AN XY: 70282

African (AFR) AF: 0.583 AC: 21091 AN: 36164

American (AMR) AF: 0.789 AC: 11607 AN: 14710

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2528 AN: 3384

East Asian (EAS) AF: 0.717 AC: 3513 AN: 4898

South Asian (SAS) AF: 0.809 AC: 3798 AN: 4694

European-Finnish (FIN) AF: 0.806 AC: 8261 AN: 10252

Middle Eastern (MID) AF: 0.783 AC: 227 AN: 290

European-Non Finnish (NFE) AF: 0.766 AC: 50847 AN: 66340

Other (OTH) AF: 0.759 AC: 1545 AN: 2036

Alfa AF: 0.709 Hom.: 4198

Bravo AF: 0.678

Asia WGS AF: 0.735 AC: 2557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61

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

Other links and lift over

dbSNP: rs2307973; hg19: chr3-12229515;