Variant rs17881652 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002083.4(GPX2):c.377C>T(p.Pro126Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,614,150 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.010 ( 13 hom., cov: 32)

Exomes 𝑓: 0.011 ( 117 hom. )

Consequence

GPX2
NM_002083.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

GPX2 (HGNC:4554): (glutathione peroxidase 2) The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is predominantly expressed in the gastrointestinal tract (also in liver in human), is localized in the cytoplasm, and whose preferred substrate is hydrogen peroxide. Overexpression of this gene is associated with increased differentiation and proliferation in colorectal cancer. This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]

GPX2 links:

CHURC1-FNTB (HGNC:):

CHURC1-FNTB links:

CHURC1 (HGNC:20099): (churchill domain containing 1) Predicted to enable zinc ion binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

CHURC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006166607).

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPX2	NM_002083.4 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	2/2	ENST00000389614.6	NP_002074.2
CHURC1-FNTB	NM_001202559.1 linkuse as main transcript	c.327+13604G>A		intron_variant			NP_001189488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPX2	ENST00000389614.6 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	2/2	1	NM_002083.4	ENSP00000374265	P1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1564

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00964

AC:

2406

AN:

249570

Hom.:

AF XY:

0.00985

AC XY:

1333

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.00851

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00418

Gnomad FIN exome

AF:

0.0202

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.00825

GnomAD4 exome

AF:

0.0113

AC:

16524

AN:

1461886

Hom.:

117

Cov.:

AF XY:

0.0111

AC XY:

8088

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.00897

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00422

Gnomad4 FIN exome

AF:

0.0202

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.00955

GnomAD4 genome

AF:

0.0103

AC:

1564

AN:

152264

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

797

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00279

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0232

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00972

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00350

AC:

ESP6500EA

AF:

0.0114

AC:

ExAC

AF:

0.00964

AC:

1166

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0130

EpiControl

AF:

0.0122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.078

T;T;.

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D;D

MetaRNN

Benign

0.0062

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.8

.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-9.3

.;D;D

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

.;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.45

MVP

0.78

MPC

0.82

ClinPred

0.077

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over