chr4-184009844-A-C

Position:

• chr4-184009844-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020225.3(STOX2):​c.1006A>C​(p.Lys336Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STOX2 NM_020225.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STOX2	NM_020225.3	c.1006A>C	p.Lys336Gln	missense_variant	3/4	ENST00000308497.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOX2	ENST00000308497.9	c.1006A>C	p.Lys336Gln	missense_variant	3/4	1	NM_020225.3	P1
STOX2	ENST00000513034.3	c.518-7245A>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.1006A>C (p.K336Q) alteration is located in exon 3 (coding exon 3) of the STOX2 gene. This alteration results from a A to C substitution at nucleotide position 1006, causing the lysine (K) at amino acid position 336 to be replaced by a glutamine (Q). 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	Uncertain	0.44
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.64
MutPred		0.31		Loss of methylation at K336 (P = 0.0118);
MVP		0.13
MPC		0.57
ClinPred		0.93	D
GERP RS		6.1
Varity_R		0.51
gMVP		0.11

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: chr4-184930997;