rs758770545

Variant names:

• chr14-81277078-C-A
• rs758770545
• NM_001394390.1:c.2404G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-81277078-C-A
• chr14-81277078-C-G
• chr14-81277078-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394390.1(STON2):​c.2404G>T​(p.Glu802*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STON2 NM_001394390.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88
• Publications: 2 publications found

Genes affected

STON2 (HGNC:30652): (stonin 2) This gene encodes a protein which is a membrane protein involved in regulating endocytotic complexes. The protein product is described as one of the clathrin-associated sorting proteins, adaptor molecules which ensure specific proteins are internalized. The encoded protein has also been shown to participate in synaptic vesicle recycling through interaction with synaptotagmin 1 required for neurotransmission. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394390.1. 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
	STON2	NM_001394390.1	MANE Select	c.2404G>T	p.Glu802*	stop_gained	Exon 6 of 8	NP_001381319.1	H0YJ05
	STON2	NM_001366849.2		c.2404G>T	p.Glu802*	stop_gained	Exon 7 of 9	NP_001353778.1	A0A3B3IU55
	STON2	NM_001256430.3		c.2233G>T	p.Glu745*	stop_gained	Exon 6 of 8	NP_001243359.1	Q8WXE9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STON2	ENST00000614646.5	TSL:5 MANE Select	c.2404G>T	p.Glu802*	stop_gained	Exon 6 of 8	ENSP00000477736.2	H0YJ05
	STON2	ENST00000555447.5	TSL:1	c.2233G>T	p.Glu745*	stop_gained	Exon 6 of 8	ENSP00000450857.1	Q8WXE9-3
	STON2	ENST00000555284.1	TSL:1	n.1741G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251486 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	44
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		7.9
Vest4		0.40
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=22/178	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: 2

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

Other links and lift over

dbSNP: rs758770545; hg19: chr14-81743422; COSMIC: COSV50856638; COSMIC: COSV50856638;