rs290198

Variant names:

• chr11-85708624-T-C
• rs290198
• NM_206927.4:c.5915+707A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206927.4(SYTL2):​c.5915+707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,784 control chromosomes in the GnomAD database, including 12,967 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 0.40 (12967 hom., cov: 30)
• Consequence: SYTL2 NM_206927.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 5 publications found

Genes affected

SYTL2 (HGNC:15585): (synaptotagmin like 2) The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTP-bound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27A-dependent vesicle trafficking and controls melanosome distribution in the cell periphery. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jun 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL2	NM_206927.4	c.5915+707A>G		intron_variant	Intron 14 of 19	ENST00000359152.10	NP_996810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL2	ENST00000359152.10	c.5915+707A>G		intron_variant	Intron 14 of 19	1	NM_206927.4	ENSP00000352065.7

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61167 AN: 151666 Hom.: 12960 Cov.: 30

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.403 AC: 61187 AN: 151784 Hom.: 12967 Cov.: 30 AF XY: 0.401 AC XY: 29723 AN XY: 74160

African (AFR) AF: 0.289 AC: 11973 AN: 41380

American (AMR) AF: 0.431 AC: 6566 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1553 AN: 3466

East Asian (EAS) AF: 0.576 AC: 2969 AN: 5158

South Asian (SAS) AF: 0.453 AC: 2185 AN: 4820

European-Finnish (FIN) AF: 0.344 AC: 3610 AN: 10492

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30971 AN: 67916

Other (OTH) AF: 0.420 AC: 888 AN: 2112

Alfa AF: 0.428 Hom.: 19866

Bravo AF: 0.402

Asia WGS AF: 0.484 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.71
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

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: rs290198; hg19: chr11-85419667;