rs1205171

Variant names:

• chr19-12800526-A-G
• rs1205171
• ENST00000466174.5:n.706T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000466174.5(PRDX2):​n.706T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 786,220 control chromosomes in the GnomAD database, including 262,336 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 0.84 (54614 hom., cov: 32)
  • Exomes 𝑓: 0.80 (207722 hom.)
• Consequence: PRDX2 ENST00000466174.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 15 publications found

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]

ENSG00000267062 (HGNC:):

HOOK2 (HGNC:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX2	NM_005809.6	c.258-227T>C		intron_variant	Intron 3 of 5	ENST00000301522.3	NP_005800.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX2	ENST00000301522.3	c.258-227T>C		intron_variant	Intron 3 of 5	1	NM_005809.6	ENSP00000301522.2

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127827 AN: 152042 Hom.: 54556 Cov.: 32

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.804 AC: 510076 AN: 634060 Hom.: 207722 Cov.: 8 AF XY: 0.800 AC XY: 257871 AN XY: 322422

African (AFR) AF: 0.961 AC: 15199 AN: 15810

American (AMR) AF: 0.834 AC: 14493 AN: 17386

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 12535 AN: 14500

East Asian (EAS) AF: 0.505 AC: 15526 AN: 30752

South Asian (SAS) AF: 0.696 AC: 32757 AN: 47050

European-Finnish (FIN) AF: 0.740 AC: 22803 AN: 30796

Middle Eastern (MID) AF: 0.862 AC: 2023 AN: 2348

European-Non Finnish (NFE) AF: 0.832 AC: 369231 AN: 443950

Other (OTH) AF: 0.811 AC: 25509 AN: 31468

GnomAD4 genome AF: 0.841 AC: 127941 AN: 152160 Hom.: 54614 Cov.: 32 AF XY: 0.830 AC XY: 61749 AN XY: 74370

African (AFR) AF: 0.958 AC: 39797 AN: 41546

American (AMR) AF: 0.830 AC: 12675 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2940 AN: 3472

East Asian (EAS) AF: 0.505 AC: 2606 AN: 5160

South Asian (SAS) AF: 0.665 AC: 3203 AN: 4814

European-Finnish (FIN) AF: 0.732 AC: 7755 AN: 10594

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56055 AN: 67980

Other (OTH) AF: 0.864 AC: 1822 AN: 2108

Alfa AF: 0.839 Hom.: 90543

Bravo AF: 0.858

Asia WGS AF: 0.619 AC: 2156 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	7.9
DANN	Benign	0.80
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1205171; hg19: chr19-12911340;