11-85707430-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_206927.4(SYTL2):​c.6017G>A​(p.Arg2006Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000131 in 1,606,438 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SYTL2
NM_206927.4 missense, splice_region

Scores

5
7
7
Splicing: ADA: 0.9577
1
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.02
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYTL2NM_206927.4 linkc.6017G>A p.Arg2006Gln missense_variant, splice_region_variant Exon 15 of 20 ENST00000359152.10 NP_996810.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYTL2ENST00000359152.10 linkc.6017G>A p.Arg2006Gln missense_variant, splice_region_variant Exon 15 of 20 1 NM_206927.4 ENSP00000352065.7 A0A8J9FM55

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152120
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250758
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135536
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000131
AC:
19
AN:
1454318
Hom.:
0
Cov.:
28
AF XY:
0.00000967
AC XY:
7
AN XY:
724056
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000163
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3116G>A (p.R1039Q) alteration is located in exon 8 (coding exon 8) of the SYTL2 gene. This alteration results from a G to A substitution at nucleotide position 3116, causing the arginine (R) at amino acid position 1039 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.080
.;.;.;.;.;.;.;T;T;.;.;.;.;.;.;.
Eigen
Uncertain
0.65
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;D;D;.;.;D;D;D;D;D;D;D;.;D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Uncertain
0.73
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.34
T
MutationAssessor
Benign
1.4
.;.;.;.;.;.;.;.;L;.;.;.;.;.;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.5
.;D;.;D;D;D;D;.;D;D;D;.;D;D;D;D
REVEL
Uncertain
0.62
Sift
Uncertain
0.028
.;D;.;D;D;D;D;.;D;D;D;.;D;D;D;D
Sift4G
Uncertain
0.058
T;D;D;T;D;D;D;D;D;T;D;D;D;T;T;.
Polyphen
0.98
D;D;.;D;.;.;D;.;D;D;D;.;D;.;.;.
Vest4
0.67
MutPred
0.61
.;.;.;.;.;.;.;.;Loss of MoRF binding (P = 0.0357);.;.;.;.;.;.;.;
MVP
0.74
MPC
0.085
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.53
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.96
dbscSNV1_RF
Benign
0.68
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs770339928; hg19: chr11-85418473; API