Variant 11-85704955-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_206927.4(SYTL2):c.6092G>A(p.Arg2031His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,613,582 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 4 hom. )

Consequence

SYTL2
NM_206927.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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]

SYTL2 links:

SYTL2 (HGNC:):

SYTL2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16887906).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYTL2	NM_206927.4 linkuse as main transcript	c.6092G>A	p.Arg2031His	missense_variant	16/20	ENST00000359152.10	NP_996810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYTL2	ENST00000359152.10 linkuse as main transcript	c.6092G>A	p.Arg2031His	missense_variant	16/20	1	NM_206927.4	ENSP00000352065.7		A0A8J9FM55

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000115

AC:

AN:

251384

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000992

AC:

145

AN:

1461334

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000954

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000945

Bravo

AF:

0.0000982

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000237

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

Jun 17, 2024

The c.3191G>A (p.R1064H) alteration is located in exon 9 (coding exon 9) of the SYTL2 gene. This alteration results from a G to A substitution at nucleotide position 3191, causing the arginine (R) at amino acid position 1064 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

.;.;.;.;.;.;.;T;T;.;.;.;.;.;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.90

D;D;D;.;.;D;D;D;D;D;D;D;.;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

2.0

.;.;.;.;.;.;.;.;M;.;.;.;.;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-4.0

.;D;.;D;D;D;D;.;D;D;D;.;D;D;D

REVEL

Benign

0.16

Sift

Benign

0.083

.;T;.;T;D;D;D;.;T;D;T;.;T;T;D

Sift4G

Benign

0.069

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.95

P;D;.;P;.;.;P;.;D;B;D;.;D;.;.

Vest4

0.33

MVP

0.41

MPC

0.080

ClinPred

0.20

GERP RS

3.7

Varity_R

0.15

gMVP

0.49

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over