11-85705004-T-C

Variant names:

• chr11-85705004-T-C
• NM_206927.4:c.6043A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206927.4(SYTL2):​c.6043A>G​(p.Lys2015Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYTL2 NM_206927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

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

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=0.22909084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL2	NM_206927.4	c.6043A>G	p.Lys2015Glu	missense_variant	Exon 16 of 20	ENST00000359152.10	NP_996810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL2	ENST00000359152.10	c.6043A>G	p.Lys2015Glu	missense_variant	Exon 16 of 20	1	NM_206927.4	ENSP00000352065.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3142A>G (p.K1048E) alteration is located in exon 9 (coding exon 9) of the SYTL2 gene. This alteration results from a A to G substitution at nucleotide position 3142, causing the lysine (K) at amino acid position 1048 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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0070	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	.;.;.;.;.;.;.;T;T;.;.;.;.;.;.;.
Eigen	Benign	-0.068
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.86	D;D;D;.;.;D;D;D;D;T;D;D;.;T;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.095	.;.;.;.;.;.;.;.;N;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.18	N;N;.;N;D;D;D;.;N;D;N;.;N;D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.23	T;T;.;T;T;T;T;.;T;T;T;.;T;T;T;T
Sift4G	Benign	0.10	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.
Polyphen		0.26	B;P;.;B;.;.;B;.;P;B;B;.;P;.;.;.
Vest4		0.37
MutPred		0.55		.;.;.;.;.;.;.;.;Loss of MoRF binding (P = 9e-04);.;.;.;.;.;.;.;
MVP		0.77
MPC		0.081
ClinPred		0.81	D
GERP RS		4.3
Varity_R		0.20
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-85416047;