Variant 14-64940282-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002083.4(GPX2):c.223-444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 773,862 control chromosomes in the GnomAD database, including 56,060 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.

Frequency

Genomes: 𝑓 0.46 ( 20342 hom., cov: 31)

Exomes 𝑓: 0.32 ( 35718 hom. )

Consequence

GPX2
NM_002083.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPX2	NM_002083.4 linkuse as main transcript	c.223-444G>A		intron_variant		ENST00000389614.6
CHURC1-FNTB	NM_001202559.1 linkuse as main transcript	c.327+14202C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPX2	ENST00000389614.6 linkuse as main transcript	c.223-444G>A		intron_variant		1	NM_002083.4	P1

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70452

AN:

151788

Hom.:

20288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.804

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.434

GnomAD4 exome

AF:

0.317

AC:

197132

AN:

621956

Hom.:

35718

AF XY:

0.320

AC XY:

103713

AN XY:

324118

show subpopulations

Gnomad4 AFR exome

AF:

0.823

Gnomad4 AMR exome

AF:

0.364

Gnomad4 ASJ exome

AF:

0.384

Gnomad4 EAS exome

AF:

0.708

Gnomad4 SAS exome

AF:

0.378

Gnomad4 FIN exome

AF:

0.352

Gnomad4 NFE exome

AF:

0.274

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.465

AC:

70570

AN:

151906

Hom.:

20342

Cov.:

AF XY:

0.466

AC XY:

34612

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.805

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.713

Gnomad4 SAS

AF:

0.394

Gnomad4 FIN

AF:

0.355

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.438

Alfa

AF:

0.351

Hom.:

2417

Bravo

AF:

0.488

Asia WGS

AF:

0.560

AC:

1949

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.36

DANN

Benign

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over