11-85709507-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_206927.4(SYTL2):c.5746-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,612,764 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (5 hom.)
• Consequence: SYTL2 NM_206927.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003270
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.129

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-85709507-G-A is Benign according to our data. Variant chr11-85709507-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642241.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL2	NM_206927.4	c.5746-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000359152.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL2	ENST00000359152.10	c.5746-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_206927.4

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 281 AN: 152166 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00275

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00209 AC: 525 AN: 250606 Hom.: 0 AF XY: 0.00208 AC XY: 282 AN XY: 135492

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00438

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00183

Gnomad FIN exome AF: 0.000805

Gnomad NFE exome AF: 0.00275

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00248 AC: 3628 AN: 1460480 Hom.: 5 Cov.: 31 AF XY: 0.00245 AC XY: 1781 AN XY: 726634

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.00203

Gnomad4 ASJ exome AF: 0.00498

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00179

Gnomad4 FIN exome AF: 0.000758

Gnomad4 NFE exome AF: 0.00274

Gnomad4 OTH exome AF: 0.00252

GnomAD4 genome AF: 0.00184 AC: 280 AN: 152284 Hom.: 1 Cov.: 31 AF XY: 0.00169 AC XY: 126 AN XY: 74450

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.00275

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00302 Hom.: 1

Bravo AF: 0.00199

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00225

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

SYTL2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.0
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000033
dbscSNV1_RF	Benign	0.054
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: rs189936985; hg19: chr11-85420550;