3-12022928-GCAA-GCAACAA

Variant names:

• chr3-12022928-G-GCAA
• rs2307981
• NM_133625.6:c.377+18003_377+18005dupACA

Variant summary

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

The NM_133625.6(SYN2):​c.377+18003_377+18005dupACA 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 (33712 hom., cov: 0)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SYN2	NM_133625.6	c.377+18003_377+18005dupACA		intron_variant	Intron 1 of 12	ENST00000621198.5	NP_598328.1
SYN2	NM_003178.6	c.377+18003_377+18005dupACA		intron_variant	Intron 1 of 10		NP_003169.2
SYN2	XM_006713311.4	c.377+18003_377+18005dupACA		intron_variant	Intron 1 of 10		XP_006713374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.377+18000_377+18001insCAA		intron_variant	Intron 1 of 12	1	NM_133625.6	ENSP00000480050.1
SYN2	ENST00000620175.4	c.377+18000_377+18001insCAA		intron_variant	Intron 1 of 10	1		ENSP00000484916.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97257 AN: 151502 Hom.: 33699 Cov.: 0

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.642 AC: 97292 AN: 151620 Hom.: 33712 Cov.: 0 AF XY: 0.647 AC XY: 47968 AN XY: 74092

African (AFR) AF: 0.354 AC: 14624 AN: 41306

American (AMR) AF: 0.758 AC: 11553 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2538 AN: 3466

East Asian (EAS) AF: 0.633 AC: 3252 AN: 5134

South Asian (SAS) AF: 0.784 AC: 3779 AN: 4820

European-Finnish (FIN) AF: 0.788 AC: 8269 AN: 10500

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.748 AC: 50740 AN: 67848

Other (OTH) AF: 0.702 AC: 1480 AN: 2108

Alfa AF: 0.676 Hom.: 3915

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs2307981; hg19: chr3-12064428;