chr4-184010095-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020225.3(STOX2):ā€‹c.1257T>Gā€‹(p.Asp419Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

STOX2
NM_020225.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10
Variant links:
Genes affected
STOX2 (HGNC:25450): (storkhead box 2) This gene encodes a Storkhead-box_winged-helix domain containing protein. This protein is differentially expressed in decidual tissue and may be involved in the susceptibility to pre-eclampsia with fetal growth restriction. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.023896486).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STOX2NM_020225.3 linkuse as main transcriptc.1257T>G p.Asp419Glu missense_variant 3/4 ENST00000308497.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STOX2ENST00000308497.9 linkuse as main transcriptc.1257T>G p.Asp419Glu missense_variant 3/41 NM_020225.3 P1Q9P2F5-1
STOX2ENST00000513034.3 linkuse as main transcriptc.518-6994T>G intron_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1452420
Hom.:
0
Cov.:
40
AF XY:
0.00
AC XY:
0
AN XY:
721414
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 08, 2023The c.1257T>G (p.D419E) alteration is located in exon 3 (coding exon 3) of the STOX2 gene. This alteration results from a T to G substitution at nucleotide position 1257, causing the aspartic acid (D) at amino acid position 419 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.27
DANN
Benign
0.90
DEOGEN2
Benign
0.012
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.33
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.024
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.92
L
MutationTaster
Benign
0.99
N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.29
N
REVEL
Benign
0.16
Sift
Benign
0.55
T
Sift4G
Benign
0.32
T
Polyphen
0.0010
B
Vest4
0.043
MutPred
0.29
Loss of glycosylation at K417 (P = 0.0678);
MVP
0.043
MPC
0.24
ClinPred
0.090
T
GERP RS
-5.0
Varity_R
0.041
gMVP
0.18

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1560941266; hg19: chr4-184931248; API