chr1-202604540-C-G

Variant summary

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

The NM_177402.5(SYT2):​c.260G>C​(p.Cys87Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SYT2
NM_177402.5 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.78
Variant links:
Genes affected
SYT2 (HGNC:11510): (synaptotagmin 2) This gene encodes a synaptic vesicle membrane protein. The encoded protein is thought to function as a calcium sensor in vesicular trafficking and exocytosis. Mutations in this gene are associated with myasthenic syndrome, presynaptic, congenital, with or without motor neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]
ENSG00000226862 (HGNC:40572): (SYT2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYT2NM_177402.5 linkc.260G>C p.Cys87Ser missense_variant Exon 3 of 9 ENST00000367268.5 NP_796376.2 Q8N9I0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYT2ENST00000367268.5 linkc.260G>C p.Cys87Ser missense_variant Exon 3 of 9 1 NM_177402.5 ENSP00000356237.4 Q8N9I0
SYT2ENST00000367267.5 linkc.260G>C p.Cys87Ser missense_variant Exon 3 of 9 2 ENSP00000356236.1 Q8N9I0
ENSG00000226862ENST00000428573.1 linkn.68+205C>G intron_variant Intron 1 of 1 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jul 12, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SYT2 protein function. This variant has not been reported in the literature in individuals affected with SYT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 87 of the SYT2 protein (p.Cys87Ser). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.70
BayesDel_addAF
Uncertain
0.053
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
25
DANN
Benign
0.89
DEOGEN2
Pathogenic
0.84
D;D
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.89
.;D
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.53
D;D
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.9
M;M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-4.2
D;D
REVEL
Benign
0.19
Sift
Benign
0.49
T;T
Sift4G
Benign
0.092
T;T
Polyphen
0.44
B;B
Vest4
0.67
MutPred
0.38
Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP
0.068
MPC
0.24
ClinPred
0.96
D
GERP RS
5.0
Varity_R
0.56
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr1-202573668; API