1-202596619-AAAAC-A

Position:

• chr1-202596619-AAAAC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_177402.5(SYT2):​c.*134_*137delGTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 827,544 control chromosomes in the GnomAD database, including 10,953 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3705 hom., cov: 28)
  • Exomes 𝑓: 0.11 (7248 hom.)
• Consequence: SYT2 NM_177402.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-202596619-AAAAC-A is Benign according to our data. Variant chr1-202596619-AAAAC-A is described in ClinVar as [Benign]. Clinvar id is 1296030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT2	NM_177402.5	c.*134_*137delGTTT		3_prime_UTR_variant	9/9	ENST00000367268.5	NP_796376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT2	ENST00000367268.5	c.*134_*137delGTTT		3_prime_UTR_variant	9/9	1	NM_177402.5	ENSP00000356237.4
SYT2	ENST00000367267.5	c.*134_*137delGTTT		3_prime_UTR_variant	9/9	2		ENSP00000356236.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 26816 AN: 148424 Hom.: 3681 Cov.: 28

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.110 AC: 74358 AN: 679002 Hom.: 7248 AF XY: 0.112 AC XY: 38410 AN XY: 344230

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.0867

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.0980

Gnomad4 NFE exome AF: 0.0663

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.181 AC: 26885 AN: 148542 Hom.: 3705 Cov.: 28 AF XY: 0.186 AC XY: 13517 AN XY: 72822

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.0928

Gnomad4 NFE AF: 0.0672

Gnomad4 OTH AF: 0.151

Alfa AF: 0.137 Hom.: 237

Bravo AF: 0.192

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs138552846; hg19: chr1-202565747;