11-85711173-C-G

Variant names:

• chr11-85711173-C-G
• rs117681965
• NM_206927.4:c.5685G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.85
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 714262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL2	NM_206927.4	c.5685G>C	p.Lys1895Asn	missense_variant	Exon 13 of 20	ENST00000359152.10	NP_996810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL2	ENST00000359152.10	c.5685G>C	p.Lys1895Asn	missense_variant	Exon 13 of 20	1	NM_206927.4	ENSP00000352065.7

Frequencies

GnomAD3 genomes AF: 0.00157 AC: 239 AN: 152168 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00199 AC: 501 AN: 251446 AF XY: 0.00193

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 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.: 6 Cov.: 30 AF XY: 0.00211 AC XY: 1531 AN XY: 727176

African (AFR) AF: 0.000418 AC: 14 AN: 33476

American (AMR) AF: 0.000470 AC: 21 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00245 AC: 64 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00676 AC: 361 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5760

European-Non Finnish (NFE) AF: 0.00229 AC: 2543 AN: 1111880

Other (OTH) AF: 0.00190 AC: 115 AN: 60394

GnomAD4 genome AF: 0.00157 AC: 239 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.00171 AC XY: 127 AN XY: 74464

African (AFR) AF: 0.000361 AC: 15 AN: 41570

American (AMR) AF: 0.000196 AC: 3 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00519 AC: 55 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00222 AC: 151 AN: 68012

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00165 Hom.: 1

Bravo AF: 0.00134

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00221 AC: 19

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

Submissions by phenotype

not provided Benign:1

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;.;.;.;.;.;T;.;.;.;T;T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;.;.;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.0088	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	.;.;.;.;.;.;M;.;.;.;.;.;.
PhyloP100		2.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.8	.;.;D;D;D;D;D;D;.;D;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0050	.;.;D;D;D;D;D;D;.;D;D;D;D
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	T
GERP RS		6.1
Varity_R		0.34
gMVP		0.36
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs117681965; hg19: chr11-85422216;