11-85707441-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_206927.4(SYTL2):c.6006C>T(p.Asn2002=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000621 in 1,612,848 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (8 hom.)
• Consequence: SYTL2 NM_206927.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.412

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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-85707441-G-A is Benign according to our data. Variant chr11-85707441-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.412 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL2	NM_206927.4	c.6006C>T	p.Asn2002=	synonymous_variant	15/20	ENST00000359152.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL2	ENST00000359152.10	c.6006C>T	p.Asn2002=	synonymous_variant	15/20	1	NM_206927.4

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.000641 AC: 161 AN: 251174 Hom.: 0 AF XY: 0.000604 AC XY: 82 AN XY: 135762

Gnomad AFR exome AF: 0.00394

Gnomad AMR exome AF: 0.000986

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000551 AC: 805 AN: 1460628 Hom.: 8 Cov.: 30 AF XY: 0.000524 AC XY: 381 AN XY: 726676

Gnomad4 AFR exome AF: 0.00673

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000316

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.00129 AC: 196 AN: 152220 Hom.: 1 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74450

Gnomad4 AFR AF: 0.00381

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.000716 Hom.: 0

Bravo AF: 0.00143

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000830

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

Nov 01, 2022

SYTL2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	2.9
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs112099986; hg19: chr11-85418484;