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.

1-202602977-GCCC-GC

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