Variant 19-12800977-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005809.6(PRDX2):c.196C>T(p.Arg66Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,612,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PRDX2
NM_005809.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

Variant links:

Genes affected

PRDX2 (HGNC:9353): (peroxiredoxin 2) This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein plays an antioxidant protective role in cells, and it may contribute to the antiviral activity of CD8(+) T-cells. The crystal structure of this protein has been resolved to 2.7 angstroms. This protein prevents hemolytic anemia from oxidative stress by stabilizing hemoglobin, thus making this gene a therapeutic target for patients with hemolytic anemia. This protein may have a proliferative effect and play a role in cancer development or progression. Related pseudogenes have been identified on chromosomes 5, 6, 10 and 13. [provided by RefSeq, Mar 2013]

PRDX2 links:

PRDX2 (HGNC:):

PRDX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39136323).

BS2

High AC in GnomAdExome4 at 162 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDX2	NM_005809.6 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	3/6	ENST00000301522.3	NP_005800.3	P32119-1V9HW12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDX2	ENST00000301522.3 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	3/6	1	NM_005809.6	ENSP00000301522.2		P32119-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

249642

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135008

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

162

AN:

1460086

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

726244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151942

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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

Jul 05, 2024

The c.196C>T (p.R66C) alteration is located in exon 3 (coding exon 2) of the PRDX2 gene. This alteration results from a C to T substitution at nucleotide position 196, causing the arginine (R) at amino acid position 66 to be replaced by a cysteine (C). 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

Benign

0.21

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.077

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.056

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

.;M

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Benign

0.13

Sift

Benign

0.064

T;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.049

.;B

Vest4

0.34

MVP

0.67

MPC

0.57

ClinPred

0.79

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.62

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