19-12800471-T-C

Position:

• chr19-12800471-T-C

Variant summary

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

The NM_005809.6(PRDX2):​c.258-172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 909,506 control chromosomes in the GnomAD database, including 12,083 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 0.21 (5584 hom., cov: 31)
  • Exomes 𝑓: 0.11 (6499 hom.)
• Consequence: PRDX2 NM_005809.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDX2	NM_005809.6	c.258-172A>G		intron_variant		ENST00000301522.3	NP_005800.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDX2	ENST00000301522.3	c.258-172A>G		intron_variant		1	NM_005809.6	ENSP00000301522.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32108 AN: 151930 Hom.: 5561 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.113 AC: 85968 AN: 757458 Hom.: 6499 Cov.: 10 AF XY: 0.112 AC XY: 42952 AN XY: 382220

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.0933

Gnomad4 EAS exome AF: 0.0753

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0788

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.212 AC: 32174 AN: 152048 Hom.: 5584 Cov.: 31 AF XY: 0.206 AC XY: 15352 AN XY: 74354

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0913

Gnomad4 EAS AF: 0.0604

Gnomad4 SAS AF: 0.0939

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.174

Alfa AF: 0.178 Hom.: 1041

Bravo AF: 0.230

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs10427027; hg19: chr19-12911285;