1-202596920-CCCAGCTTGTCATAGT-C

Position:

• chr1-202596920-CCCAGCTTGTCATAGT-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PM4 PP3 PP5

The NM_177402.5(SYT2):​c.1082_1096delACTATGACAAGCTGG​(p.Asp361_Leu365del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SYT2 NM_177402.5 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.25

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 Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a region_of_interest Phospholipid binding (size 246) in uniprot entity SYT2_HUMAN there are 9 pathogenic changes around while only 0 benign (100%) in NM_177402.5
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_177402.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 1-202596920-CCCAGCTTGTCATAGT-C is Pathogenic according to our data. Variant chr1-202596920-CCCAGCTTGTCATAGT-C is described in ClinVar as [Pathogenic]. Clinvar id is 1192312.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT2	NM_177402.5	c.1082_1096delACTATGACAAGCTGG	p.Asp361_Leu365del	disruptive_inframe_deletion	9/9	ENST00000367268.5	NP_796376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT2	ENST00000367268.5	c.1082_1096delACTATGACAAGCTGG	p.Asp361_Leu365del	disruptive_inframe_deletion	9/9	1	NM_177402.5	ENSP00000356237.4
SYT2	ENST00000367267.5	c.1082_1096delACTATGACAAGCTGG	p.Asp361_Leu365del	disruptive_inframe_deletion	9/9	2		ENSP00000356236.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital myasthenic syndrome 7 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-202566048;