chr14-81270732-A-C

Variant names:

• chr14-81270732-A-C
• rs2241621
• NM_001394390.1:c.2722T>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.2722T>G​(p.Ser908Ala) variant causes a missense change. The variant allele was found at a frequency of 0.558 in 1,613,772 control chromosomes in the GnomAD database, including 256,448 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 0.48 (18662 hom., cov: 32)
  • Exomes 𝑓: 0.57 (237786 hom.)
• Consequence: STON2 NM_001394390.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.34
• Publications: 33 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 (MetaRNN=0.0016493797).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 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.2722T>G	p.Ser908Ala	missense	Exon 7 of 8	NP_001381319.1	H0YJ05
	STON2	NM_001366849.2		c.2722T>G	p.Ser908Ala	missense	Exon 8 of 9	NP_001353778.1	A0A3B3IU55
	STON2	NM_001256430.3		c.2551T>G	p.Ser851Ala	missense	Exon 7 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.2722T>G	p.Ser908Ala	missense	Exon 7 of 8	ENSP00000477736.2	H0YJ05
	STON2	ENST00000555447.5	TSL:1	c.2551T>G	p.Ser851Ala	missense	Exon 7 of 8	ENSP00000450857.1	Q8WXE9-3
	STON2	ENST00000555284.1	TSL:1	n.2059T>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72509 AN: 151854 Hom.: 18663 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.520

GnomAD2 exomes AF: 0.524 AC: 131729 AN: 251472 AF XY: 0.535

Gnomad AFR exome AF: 0.275

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.582

Gnomad EAS exome AF: 0.384

Gnomad FIN exome AF: 0.505

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.560

GnomAD4 exome AF: 0.566 AC: 828108 AN: 1461800 Hom.: 237786 Cov.: 52 AF XY: 0.568 AC XY: 412989 AN XY: 727204

African (AFR) AF: 0.269 AC: 9021 AN: 33480

American (AMR) AF: 0.475 AC: 21230 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 15203 AN: 26132

East Asian (EAS) AF: 0.433 AC: 17174 AN: 39700

South Asian (SAS) AF: 0.569 AC: 49090 AN: 86256

European-Finnish (FIN) AF: 0.501 AC: 26767 AN: 53414

Middle Eastern (MID) AF: 0.621 AC: 3583 AN: 5766

European-Non Finnish (NFE) AF: 0.588 AC: 653343 AN: 1111938

Other (OTH) AF: 0.541 AC: 32697 AN: 60394

GnomAD4 genome AF: 0.477 AC: 72517 AN: 151972 Hom.: 18662 Cov.: 32 AF XY: 0.477 AC XY: 35392 AN XY: 74274

African (AFR) AF: 0.283 AC: 11728 AN: 41452

American (AMR) AF: 0.499 AC: 7616 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2002 AN: 3464

East Asian (EAS) AF: 0.389 AC: 2004 AN: 5148

South Asian (SAS) AF: 0.550 AC: 2651 AN: 4816

European-Finnish (FIN) AF: 0.499 AC: 5273 AN: 10562

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39492 AN: 67964

Other (OTH) AF: 0.515 AC: 1085 AN: 2106

Alfa AF: 0.547 Hom.: 80132

Bravo AF: 0.467

TwinsUK AF: 0.596 AC: 2209

ALSPAC AF: 0.580 AC: 2236

ESP6500AA AF: 0.292 AC: 1287

ESP6500EA AF: 0.590 AC: 5070

ExAC AF: 0.522 AC: 63406

Asia WGS AF: 0.424 AC: 1475 AN: 3478

EpiCase AF: 0.597

EpiControl AF: 0.591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.13
Sift	Benign	0.044	D
Sift4G	Benign	0.37	T
Polyphen		1.0	D
Vest4		0.28
MPC		0.46
ClinPred		0.033	T
GERP RS		4.4
Varity_R		0.11
gMVP		0.19
Mutation Taster		=98/2	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: rs2241621; hg19: chr14-81737076; COSMIC: COSV50845221;