rs9323698

Variant names:

• chr14-81280366-T-C
• rs9323698
• NM_001394390.1:c.743-1627A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394390.1(STON2):​c.743-1627A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,992 control chromosomes in the GnomAD database, including 28,230 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28230 hom., cov: 31)
• Consequence: STON2 NM_001394390.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

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.743-1627A>G		intron	N/A	NP_001381319.1
	STON2	NM_001366849.2		c.743-1627A>G		intron	N/A	NP_001353778.1
	STON2	NM_001256430.3		c.572-1627A>G		intron	N/A	NP_001243359.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STON2	ENST00000614646.5	TSL:5 MANE Select	c.743-1627A>G		intron	N/A	ENSP00000477736.2
	STON2	ENST00000555447.5	TSL:1	c.572-1627A>G		intron	N/A	ENSP00000450857.1
	STON2	ENST00000649389.1		c.743-1627A>G		intron	N/A	ENSP00000498075.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91801 AN: 151874 Hom.: 28209 Cov.: 31

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.604 AC: 91852 AN: 151992 Hom.: 28230 Cov.: 31 AF XY: 0.600 AC XY: 44546 AN XY: 74296

African (AFR) AF: 0.547 AC: 22680 AN: 41426

American (AMR) AF: 0.595 AC: 9092 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2157 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2015 AN: 5148

South Asian (SAS) AF: 0.560 AC: 2697 AN: 4820

European-Finnish (FIN) AF: 0.588 AC: 6215 AN: 10562

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45112 AN: 67976

Other (OTH) AF: 0.615 AC: 1295 AN: 2106

Alfa AF: 0.647 Hom.: 134889

Bravo AF: 0.603

Asia WGS AF: 0.463 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.67
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9323698; hg19: chr14-81746710;