Variant 1-202596820-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_177402.5(SYT2):c.1197C>T(p.Ile399Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,613,786 control chromosomes in the GnomAD database, including 110,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9375 hom., cov: 32)

Exomes 𝑓: 0.37 ( 100715 hom. )

Consequence

SYT2
NM_177402.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.544

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]

SYT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 1-202596820-G-A is Benign according to our data. Variant chr1-202596820-G-A is described in ClinVar as [Benign]. Clinvar id is 1226268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-202596820-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.544 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT2	NM_177402.5 linkuse as main transcript	c.1197C>T	p.Ile399Ile	synonymous_variant	9/9	ENST00000367268.5	NP_796376.2	Q8N9I0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT2	ENST00000367268.5 linkuse as main transcript	c.1197C>T	p.Ile399Ile	synonymous_variant	9/9	1	NM_177402.5	ENSP00000356237.4		Q8N9I0
SYT2	ENST00000367267.5 linkuse as main transcript	c.1197C>T	p.Ile399Ile	synonymous_variant	9/9	2		ENSP00000356236.1		Q8N9I0

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52712

AN:

151950

Hom.:

9368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.351

GnomAD3 exomes

AF:

0.343

AC:

86206

AN:

251258

Hom.:

15355

AF XY:

0.348

AC XY:

47219

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.317

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.434

Gnomad EAS exome

AF:

0.315

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.380

Gnomad OTH exome

AF:

0.362

GnomAD4 exome

AF:

0.368

AC:

538590

AN:

1461720

Hom.:

100715

Cov.:

AF XY:

0.368

AC XY:

267375

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.314

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.437

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.322

Gnomad4 FIN exome

AF:

0.382

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.365

GnomAD4 genome

AF:

0.347

AC:

52739

AN:

152066

Hom.:

9375

Cov.:

AF XY:

0.345

AC XY:

25661

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.313

Gnomad4 AMR

AF:

0.273

Gnomad4 ASJ

AF:

0.458

Gnomad4 EAS

AF:

0.299

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.379

Gnomad4 NFE

AF:

0.379

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.375

Hom.:

6175

Bravo

AF:

0.339

Asia WGS

AF:

0.307

AC:

1068

AN:

3478

EpiCase

AF:

0.379

EpiControl

AF:

0.379

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

6.1

DANN

Benign

0.87

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