rs17111687

Variant names:

• chr14-81297134-G-A
• rs17111687
• NM_001394390.1:c.743-18395C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001394390.1(STON2):​c.743-18395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 152,202 control chromosomes in the GnomAD database, including 69 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 0.016 (69 hom., cov: 32)
• Consequence: STON2 NM_001394390.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 1 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=-0.94).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0165 (2509/152202) while in subpopulation AFR AF = 0.0505 (2097/41512). AF 95% confidence interval is 0.0487. There are 69 homozygotes in GnomAd4. There are 1174 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 69 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STON2	NM_001394390.1	c.743-18395C>T		intron_variant	Intron 5 of 7	ENST00000614646.5	NP_001381319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STON2	ENST00000614646.5	c.743-18395C>T		intron_variant	Intron 5 of 7	5	NM_001394390.1	ENSP00000477736.2

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2508 AN: 152084 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00204

Gnomad OTH AF: 0.0182

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

GnomAD4 genome AF: 0.0165 AC: 2509 AN: 152202 Hom.: 69 Cov.: 32 AF XY: 0.0158 AC XY: 1174 AN XY: 74428

African (AFR) AF: 0.0505 AC: 2097 AN: 41512

American (AMR) AF: 0.0118 AC: 181 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00204 AC: 139 AN: 68002

Other (OTH) AF: 0.0180 AC: 38 AN: 2106

Alfa AF: 0.0171 Hom.: 8

Bravo AF: 0.0188

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.53
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs17111687; hg19: chr14-81763478;