14-81278392-A-G

Position:

• chr14-81278392-A-G

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STON2	NM_001394390.1	c.1090T>C	p.Ser364Pro	missense_variant	6/8	ENST00000614646.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STON2	ENST00000614646.5	c.1090T>C	p.Ser364Pro	missense_variant	6/8	5	NM_001394390.1	P1

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

GnomAD3 exomes AF: 0.810 AC: 203718 AN: 251456 Hom.: 83414 AF XY: 0.808 AC XY: 109749 AN XY: 135904

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 SAS exome AF: 0.747

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

Gnomad4 AFR exome AF: 0.846

Gnomad4 AMR exome AF: 0.834

Gnomad4 ASJ exome AF: 0.894

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.746

Gnomad4 FIN exome AF: 0.783

Gnomad4 NFE exome AF: 0.852

Gnomad4 OTH exome AF: 0.814

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

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.822

Alfa AF: 0.846 Hom.: 140747

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.13
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.035	N
MetaRNN	Benign	6.0e-7	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.1	N;.;N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.3	N;.;.;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;.;.;T
Sift4G	Benign	0.93	T;.;T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3813535; hg19: chr14-81744736; COSMIC: COSV50842352; COSMIC: COSV50842352;