NM_206927.4:c.5626-925C>A

Variant names:

• chr11-85712157-G-T
• rs290202
• NM_206927.4:c.5626-925C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.55).
• 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 rank	MANE	Protein	UniProt
SYTL2	NM_206927.4	c.5626-925C>A		intron_variant	Intron 12 of 19	ENST00000359152.10	NP_996810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL2	ENST00000359152.10	c.5626-925C>A		intron_variant	Intron 12 of 19	1	NM_206927.4	ENSP00000352065.7

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

African (AFR) AF: 0.452 AC: 18730 AN: 41418

American (AMR) AF: 0.547 AC: 8346 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2151 AN: 3466

East Asian (EAS) AF: 0.609 AC: 3143 AN: 5164

South Asian (SAS) AF: 0.494 AC: 2380 AN: 4814

European-Finnish (FIN) AF: 0.673 AC: 7111 AN: 10566

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43185 AN: 67970

Other (OTH) AF: 0.577 AC: 1216 AN: 2108

Alfa AF: 0.592 Hom.: 4109

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
PhyloP100		0.90
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: rs290202; hg19: chr11-85423200;