14-81277059-T-G

Variant names:

• chr14-81277059-T-G
• rs147885542
• NM_001394390.1:c.2423A>C

Variant summary

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

The NM_001394390.1(STON2):​c.2423A>C​(p.Lys808Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: STON2 NM_001394390.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1803154).

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.2423A>C	p.Lys808Thr	missense	Exon 6 of 8	NP_001381319.1	H0YJ05
	STON2	NM_001366849.2		c.2423A>C	p.Lys808Thr	missense	Exon 7 of 9	NP_001353778.1	A0A3B3IU55
	STON2	NM_001256430.3		c.2252A>C	p.Lys751Thr	missense	Exon 6 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.2423A>C	p.Lys808Thr	missense	Exon 6 of 8	ENSP00000477736.2	H0YJ05
	STON2	ENST00000555447.5	TSL:1	c.2252A>C	p.Lys751Thr	missense	Exon 6 of 8	ENSP00000450857.1	Q8WXE9-3
	STON2	ENST00000555284.1	TSL:1	n.1760A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.0000278 AC: 7 AN: 251492 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000287 AC: 42 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1112010

Other (OTH) AF: 0.0000828 AC: 5 AN: 60396

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74472

African (AFR) AF: 0.0000722 AC: 3 AN: 41570

American (AMR) AF: 0.000654 AC: 10 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.000332

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.21
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.54
MVP		0.18
MPC		0.55
ClinPred		0.63	D
GERP RS		5.9
Varity_R		0.33
gMVP		0.56
Mutation Taster		=72/28	polymorphism

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: rs147885542; hg19: chr14-81743403;