Genetic Variant SYT2:c.465+20_465+21delGG (chr1-202602977-GCC-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_177402.5(SYT2):c.465+20_465+21delGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,583,192 control chromosomes in the GnomAD database, including 295,396 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 27352 hom., cov: 0)

Exomes 𝑓: 0.61 ( 268044 hom. )

Consequence

SYT2
NM_177402.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.00

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 -16 ACMG points.

BP6

Variant 1-202602977-GCC-G is Benign according to our data. Variant chr1-202602977-GCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 445706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-202602977-GCC-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT2	NM_177402.5 link	c.465+20_465+21delGG		intron_variant	Intron 4 of 8	ENST00000367268.5	NP_796376.2	Q8N9I0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT2	ENST00000367268.5 link	c.465+20_465+21delGG		intron_variant	Intron 4 of 8	1	NM_177402.5	ENSP00000356237.4		Q8N9I0
SYT2	ENST00000367267.5 link	c.465+20_465+21delGG		intron_variant	Intron 4 of 8	2		ENSP00000356236.1		Q8N9I0

Frequencies

GnomAD3 genomes

AF:

0.610

AC:

90199

AN:

147814

Hom.:

27322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.566

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.706

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.698

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.606

Gnomad OTH

AF:

0.611

GnomAD3 exomes

AF:

0.646

AC:

156800

AN:

242710

Hom.:

50205

AF XY:

0.643

AC XY:

84338

AN XY:

131142

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.780

Gnomad ASJ exome

AF:

0.575

Gnomad EAS exome

AF:

0.695

Gnomad SAS exome

AF:

0.672

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.615

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.612

AC:

879082

AN:

1435262

Hom.:

268044

AF XY:

0.614

AC XY:

437037

AN XY:

711272

show subpopulations

Gnomad4 AFR exome

AF:

0.555

Gnomad4 AMR exome

AF:

0.768

Gnomad4 ASJ exome

AF:

0.560

Gnomad4 EAS exome

AF:

0.711

Gnomad4 SAS exome

AF:

0.667

Gnomad4 FIN exome

AF:

0.622

Gnomad4 NFE exome

AF:

0.601

Gnomad4 OTH exome

AF:

0.610

GnomAD4 genome

AF:

0.610

AC:

90281

AN:

147930

Hom.:

27352

Cov.:

AF XY:

0.614

AC XY:

44228

AN XY:

72052

show subpopulations

Gnomad4 AFR

AF:

0.566

Gnomad4 AMR

AF:

0.707

Gnomad4 ASJ

AF:

0.532

Gnomad4 EAS

AF:

0.699

Gnomad4 SAS

AF:

0.674

Gnomad4 FIN

AF:

0.627

Gnomad4 NFE

AF:

0.606

Gnomad4 OTH

AF:

0.613

Alfa

AF:

0.523

Hom.:

2466

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 23, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital myasthenic syndrome 7

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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