chr14-81278392-A-G

Variant names:

• chr14-81278392-A-G
• rs3813535
• NM_001394390.1:c.1090T>C

Variant summary

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

The NM_001394390.1(STON2):​c.1090T>C​(p.Ser364Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,614,034 control chromosomes in the GnomAD database, including 564,480 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.83 (52348 hom., cov: 32)
  • Exomes 𝑓: 0.84 (512132 hom.)
• Consequence: STON2 NM_001394390.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28
• 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=6.0004425E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STON2	NM_001394390.1	MANE Select	c.1090T>C	p.Ser364Pro	missense	Exon 6 of 8	NP_001381319.1
	STON2	NM_001366849.2		c.1090T>C	p.Ser364Pro	missense	Exon 7 of 9	NP_001353778.1
	STON2	NM_001256430.3		c.919T>C	p.Ser307Pro	missense	Exon 6 of 8	NP_001243359.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STON2	ENST00000614646.5	TSL:5 MANE Select	c.1090T>C	p.Ser364Pro	missense	Exon 6 of 8	ENSP00000477736.2
	STON2	ENST00000555447.5	TSL:1	c.919T>C	p.Ser307Pro	missense	Exon 6 of 8	ENSP00000450857.1
	STON2	ENST00000555284.1	TSL:1	n.427T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125773 AN: 152054 Hom.: 52322 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.830

GnomAD2 exomes AF: 0.810 AC: 203718 AN: 251456 AF XY: 0.808

Gnomad AFR exome AF: 0.846

Gnomad AMR exome AF: 0.838

Gnomad ASJ exome AF: 0.892

Gnomad EAS exome AF: 0.557

Gnomad FIN exome AF: 0.784

Gnomad NFE exome AF: 0.851

Gnomad OTH exome AF: 0.832

GnomAD4 exome AF: 0.835 AC: 1221214 AN: 1461862 Hom.: 512132 Cov.: 66 AF XY: 0.833 AC XY: 605716 AN XY: 727236

African (AFR) AF: 0.846 AC: 28326 AN: 33478

American (AMR) AF: 0.834 AC: 37322 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 23371 AN: 26136

East Asian (EAS) AF: 0.632 AC: 25080 AN: 39700

South Asian (SAS) AF: 0.746 AC: 64344 AN: 86258

European-Finnish (FIN) AF: 0.783 AC: 41822 AN: 53418

Middle Eastern (MID) AF: 0.828 AC: 4776 AN: 5768

European-Non Finnish (NFE) AF: 0.852 AC: 947013 AN: 1111986

Other (OTH) AF: 0.814 AC: 49160 AN: 60394

GnomAD4 genome AF: 0.827 AC: 125845 AN: 152172 Hom.: 52348 Cov.: 32 AF XY: 0.819 AC XY: 60955 AN XY: 74392

African (AFR) AF: 0.846 AC: 35098 AN: 41504

American (AMR) AF: 0.804 AC: 12300 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3088 AN: 3472

East Asian (EAS) AF: 0.580 AC: 3005 AN: 5180

South Asian (SAS) AF: 0.725 AC: 3492 AN: 4816

European-Finnish (FIN) AF: 0.785 AC: 8295 AN: 10570

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.850 AC: 57842 AN: 68018

Other (OTH) AF: 0.822 AC: 1736 AN: 2112

Alfa AF: 0.845 Hom.: 264151

Bravo AF: 0.832

TwinsUK AF: 0.854 AC: 3168

ALSPAC AF: 0.848 AC: 3268

ESP6500AA AF: 0.845 AC: 3722

ESP6500EA AF: 0.852 AC: 7328

ExAC AF: 0.810 AC: 98332

Asia WGS AF: 0.634 AC: 2205 AN: 3478

EpiCase AF: 0.856

EpiControl AF: 0.847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.13
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.023	T
MetaRNN	Benign	6.0e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.1	N
PhyloP100		3.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.055
MPC		0.13
ClinPred		0.010	T
GERP RS		6.2
Varity_R		0.31
gMVP		0.22
Mutation Taster		=97/3	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: rs3813535; hg19: chr14-81744736; COSMIC: COSV50842352; COSMIC: COSV50842352;