1-202602977-GCCC-G

Variant names:

• chr1-202602977-GCCC-G
• rs55968420
• NM_177402.5:c.465+19_465+21delGGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_177402.5(SYT2):​c.465+19_465+21delGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYT2 NM_177402.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177402.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT2	NM_177402.5	MANE Select	c.465+19_465+21delGGG		intron	N/A	NP_796376.2
	SYT2	NM_001136504.1		c.465+19_465+21delGGG		intron	N/A	NP_001129976.1	Q8N9I0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT2	ENST00000367268.5	TSL:1 MANE Select	c.465+19_465+21delGGG		intron	N/A	ENSP00000356237.4	Q8N9I0
	SYT2	ENST00000930883.1		c.525+19_525+21delGGG		intron	N/A	ENSP00000600942.1
	SYT2	ENST00000899895.1		c.474+19_474+21delGGG		intron	N/A	ENSP00000569954.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1435444 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 711376

African (AFR) AF: 0.00 AC: 0 AN: 32758

American (AMR) AF: 0.00 AC: 0 AN: 43246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39008

South Asian (SAS) AF: 0.00 AC: 0 AN: 82958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095296

Other (OTH) AF: 0.00 AC: 0 AN: 59038

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs55968420; hg19: chr1-202572105;