11-85712157-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206927.4(SYTL2):c.5626-925C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,970 control chromosomes in the GnomAD database, including 25,463 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 0.57 (25463 hom., cov: 31)
• Consequence: SYTL2 NM_206927.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL2	NM_206927.4	c.5626-925C>A		intron_variant		ENST00000359152.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL2	ENST00000359152.10	c.5626-925C>A		intron_variant		1	NM_206927.4

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86927 AN: 151852 Hom.: 25466 Cov.: 31

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.572 AC: 86933 AN: 151970 Hom.: 25463 Cov.: 31 AF XY: 0.572 AC XY: 42491 AN XY: 74288

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.577

Alfa AF: 0.597 Hom.: 4020

Bravo AF: 0.557

Asia WGS AF: 0.524 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	13
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs290202; hg19: chr11-85423200;