Genetic Variant NM_001394390.1:c.2587G>A (chr14-81270867-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001394390.1(STON2):c.2587G>A(p.Gly863Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,612,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G863C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

STON2
NM_001394390.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.51

Publications

1 publications found

Variant links:

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]

STON2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23725623).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STON2	NM_001394390.1	MANE Select	c.2587G>A	p.Gly863Ser	missense	Exon 7 of 8	NP_001381319.1	H0YJ05
STON2	NM_001366849.2		c.2587G>A	p.Gly863Ser	missense	Exon 8 of 9	NP_001353778.1	A0A3B3IU55
STON2	NM_001256430.3		c.2416G>A	p.Gly806Ser	missense	Exon 7 of 8	NP_001243359.1	Q8WXE9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STON2	ENST00000614646.5	TSL:5 MANE Select	c.2587G>A	p.Gly863Ser	missense	Exon 7 of 8	ENSP00000477736.2	H0YJ05
STON2	ENST00000555447.5	TSL:1	c.2416G>A	p.Gly806Ser	missense	Exon 7 of 8	ENSP00000450857.1	Q8WXE9-3
STON2	ENST00000555284.1	TSL:1	n.1924G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

250602

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1460126

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726370

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33434

American (AMR)

AF:

0.0000224

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39682

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86170

European-Finnish (FIN)

AF:

0.000113

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4724

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111738

Other (OTH)

AF:

0.0000166

AC:

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000855

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.000242

AC:

AN:

41338

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.010

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

4.5

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.37

REVEL

Benign

0.16

Sift

Uncertain

0.025

Sift4G

Benign

0.082

Polyphen

1.0

Vest4

0.51

MutPred

0.58

Loss of sheet (P = 0.0181)

MVP

0.17

MPC

0.47

ClinPred

0.29

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.50

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over