rs2412065

Positions:

• chr14-64940939-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002083.4(GPX2):​c.223-1101G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,120 control chromosomes in the GnomAD database, including 6,119 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 0.27 (6119 hom., cov: 32)
• Consequence: GPX2 NM_002083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

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]

CHURC1-FNTB (HGNC:):

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]

ACMG classification

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 = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPX2	NM_002083.4	c.223-1101G>C		intron_variant		ENST00000389614.6
CHURC1-FNTB	NM_001202559.1	c.327+14859C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPX2	ENST00000389614.6	c.223-1101G>C		intron_variant		1	NM_002083.4	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40229 AN: 152002 Hom.: 6094 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.265 AC: 40317 AN: 152120 Hom.: 6119 Cov.: 32 AF XY: 0.267 AC XY: 19818 AN XY: 74362

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.241

Alfa AF: 0.237 Hom.: 601

Bravo AF: 0.270

Asia WGS AF: 0.259 AC: 900 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	11
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs2412065; hg19: chr14-65407657;