rs1205171

chr19-12800526-A-G

Variant summary

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

The NM_005809.6(PRDX2):c.258-227T>C variant causes a intron 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 NM_005809.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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]

(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

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 = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDX2	NM_005809.6	c.258-227T>C		intron_variant		ENST00000301522.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDX2	ENST00000301522.3	c.258-227T>C		intron_variant		1	NM_005809.6	P1
	ENST00000585496.1	n.201-1228A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.961

Gnomad4 AMR exome AF: 0.834

Gnomad4 ASJ exome AF: 0.864

Gnomad4 EAS exome AF: 0.505

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.740

Gnomad4 NFE exome AF: 0.832

Gnomad4 OTH exome AF: 0.811

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

Gnomad4 AFR AF: 0.958

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.864

Alfa AF: 0.834 Hom.: 70630

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

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: rs1205171; hg19: chr19-12911340;