Variant 11-85711173-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_206927.4(SYTL2):c.5685G>C(p.Lys1895Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,614,008 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 6 hom. )

Consequence

SYTL2
NM_206927.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.85

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008764625).

BP6

Variant 11-85711173-C-G is Benign according to our data. Variant chr11-85711173-C-G is described in ClinVar as [Benign]. Clinvar id is 714262.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL2	NM_206927.4 linkuse as main transcript	c.5685G>C	p.Lys1895Asn	missense_variant	13/20	ENST00000359152.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL2	ENST00000359152.10 linkuse as main transcript	c.5685G>C	p.Lys1895Asn	missense_variant	13/20	1	NM_206927.4

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

239

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00519

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00199

AC:

501

AN:

251446

Hom.:

AF XY:

0.00193

AC XY:

262

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00688

Gnomad NFE exome

AF:

0.00260

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00213

AC:

3120

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1531

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00245

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00676

Gnomad4 NFE exome

AF:

0.00229

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152286

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00519

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00134

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00189

AC:

230

EpiCase

AF:

0.00202

EpiControl

AF:

0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.058

MetaRNN

Benign

0.0088

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

MetaSVM

Benign

-0.81

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.57

REVEL

Benign

0.21

Sift4G

Uncertain

0.018

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

Polyphen

0.99

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

Vest4

0.28

MutPred

0.25

.;.;.;.;.;.;Loss of ubiquitination at K590 (P = 0.0067);.;.;.;.;.;.;

MVP

0.57

MPC

0.094

ClinPred

0.057

GERP RS

6.1

Varity_R

0.34

gMVP

0.36

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