chr4-184009443-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020225.3(STOX2):​c.605G>A​(p.Cys202Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STOX2
NM_020225.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.19
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20357215).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STOX2NM_020225.3 linkuse as main transcriptc.605G>A p.Cys202Tyr missense_variant 3/4 ENST00000308497.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STOX2ENST00000308497.9 linkuse as main transcriptc.605G>A p.Cys202Tyr missense_variant 3/41 NM_020225.3 P1Q9P2F5-1
STOX2ENST00000513034.3 linkuse as main transcriptc.518-7646G>A intron_variant 3
STOX2ENST00000512520.1 linkuse as main transcriptc.*349G>A 3_prime_UTR_variant, NMD_transcript_variant 3/34

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461712
Hom.:
0
Cov.:
39
AF XY:
0.00
AC XY:
0
AN XY:
727138
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
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 GeneticsNov 07, 2023The c.605G>A (p.C202Y) alteration is located in exon 3 (coding exon 3) of the STOX2 gene. This alteration results from a G to A substitution at nucleotide position 605, causing the cysteine (C) at amino acid position 202 to be replaced by a tyrosine (Y). 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
0.15
BayesDel_addAF
Benign
-0.012
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
22
DANN
Benign
0.85
DEOGEN2
Benign
0.026
T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.59
T
MutationAssessor
Benign
-1.4
N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
2.0
N
REVEL
Uncertain
0.31
Sift
Benign
1.0
T
Sift4G
Benign
0.89
T
Polyphen
0.99
D
Vest4
0.29
MutPred
0.40
Gain of helix (P = 0.0854);
MVP
0.043
MPC
0.42
ClinPred
0.60
D
GERP RS
5.5
Varity_R
0.35
gMVP
0.017

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-184930596; API