chr14-64942593-C-T

Position:

chr14-64942593-C-T

Variant summary

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

The NM_002083.4(GPX2):c.134G>A(p.Arg45Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,614,082 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 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

GPX2
NM_002083.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

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 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=0.14293522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPX2	NM_002083.4 linkuse as main transcript	c.134G>A	p.Arg45Gln	missense_variant	1/2	ENST00000389614.6	NP_002074.2
CHURC1-FNTB	NM_001202559.1 linkuse as main transcript	c.327+16513C>T		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.134G>A	p.Arg45Gln	missense_variant	1/2	1	NM_002083.4	ENSP00000374265	P1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000180

AC:

AN:

249452

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000300

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000169

AC:

247

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000193

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000217

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.000208

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000503

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000215

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000593

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 submitter

clinical testing

Ambry Genetics

Jan 17, 2023

The c.134G>A (p.R45Q) alteration is located in exon 1 (coding exon 1) of the GPX2 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the arginine (R) at amino acid position 45 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

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.032

T;T

Eigen

Benign

0.077

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.5

.;D

REVEL

Benign

0.16

Sift

Benign

0.56

.;T

Sift4G

Benign

0.37

T;T

Polyphen

0.97

.;D

Vest4

0.72

MVP

0.51

MPC

0.52

ClinPred

0.10

GERP RS

4.7

Varity_R

0.34

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over