Genetic Variant SYT2:c.345+177G>A (chr1-202604278-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_177402.5(SYT2):c.345+177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 651,804 control chromosomes in the GnomAD database, including 6,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 1097 hom., cov: 32)

Exomes 𝑓: 0.11 ( 5617 hom. )

Consequence

SYT2
NM_177402.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.665

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:

ENSG00000226862 (HGNC:40572): (SYT2 antisense RNA 1)

ENSG00000226862 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-202604278-C-T is Benign according to our data. Variant chr1-202604278-C-T is described in ClinVar as [Benign]. Clinvar id is 1296027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT2	NM_177402.5 link	c.345+177G>A		intron_variant	Intron 3 of 8	ENST00000367268.5	NP_796376.2	Q8N9I0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYT2	ENST00000367268.5 link	c.345+177G>A	intron_variant	Intron 3 of 8	1	NM_177402.5	ENSP00000356237.4	Q8N9I0
SYT2	ENST00000367267.5 link	c.345+177G>A	intron_variant	Intron 3 of 8	2		ENSP00000356236.1	Q8N9I0
ENSG00000226862	ENST00000428573.1 link	n.11C>T	non_coding_transcript_exon_variant	Exon 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0958

AC:

14568

AN:

152112

Hom.:

1090

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0842

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.0818

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.0904

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0593

Gnomad OTH

AF:

0.0928

GnomAD4 exome

AF:

0.109

AC:

54525

AN:

499576

Hom.:

5617

Cov.:

AF XY:

0.110

AC XY:

29126

AN XY:

264300

show subpopulations

Gnomad4 AFR exome

AF:

0.0823

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.0790

Gnomad4 EAS exome

AF:

0.418

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.0922

Gnomad4 NFE exome

AF:

0.0588

Gnomad4 OTH exome

AF:

0.0917

GnomAD4 genome

AF:

0.0958

AC:

14587

AN:

152228

Hom.:

1097

Cov.:

AF XY:

0.103

AC XY:

7670

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0841

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.0818

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.0904

Gnomad4 NFE

AF:

0.0593

Gnomad4 OTH

AF:

0.0947

Alfa

AF:

0.0270

Hom.:

Bravo

AF:

0.100

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.4

DANN

Benign

0.47

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