chr11-85714416-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_206927.4(SYTL2):āc.5622T>Gā(p.Asp1874Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,459,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000014 ( 0 hom. )
Consequence
SYTL2
NM_206927.4 missense
NM_206927.4 missense
Scores
4
11
Clinical Significance
Conservation
PhyloP100: 2.13
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08480874).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYTL2 | NM_206927.4 | c.5622T>G | p.Asp1874Glu | missense_variant | 12/20 | ENST00000359152.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYTL2 | ENST00000359152.10 | c.5622T>G | p.Asp1874Glu | missense_variant | 12/20 | 1 | NM_206927.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251236Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135778
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1459654Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 726330
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2022 | The c.2721T>G (p.D907E) alteration is located in exon 5 (coding exon 5) of the SYTL2 gene. This alteration results from a T to G substitution at nucleotide position 2721, causing the aspartic acid (D) at amino acid position 907 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;.;.;T;T;T;T;T;T;.;T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
REVEL
Benign
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;.;.;.;.
Polyphen
B;B;.;B;.;.;.;B;B;B;.;B;.;.;.;.;.;.
Vest4
MutPred
0.16
.;.;.;.;.;.;.;Gain of MoRF binding (P = 0.3206);.;.;.;.;.;.;.;.;.;.;
MVP
MPC
0.022
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at