rs10422248

Variant names:

• chr19-12801112-C-T
• rs10422248
• NM_005809.6:c.104-43G>A

Variant summary

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

The NM_005809.6(PRDX2):​c.104-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,613,614 control chromosomes in the GnomAD database, including 1,954 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 0.067 (555 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1399 hom.)
• Consequence: PRDX2 NM_005809.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005809.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX2	NM_005809.6	MANE Select	c.104-43G>A		intron	N/A	NP_005800.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX2	ENST00000301522.3	TSL:1 MANE Select	c.104-43G>A		intron	N/A	ENSP00000301522.2
	PRDX2	ENST00000466174.5	TSL:1	n.163-43G>A		intron	N/A
	PRDX2	ENST00000866180.1		c.104-43G>A		intron	N/A	ENSP00000536239.1

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10151 AN: 152114 Hom.: 550 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0314

Gnomad OTH AF: 0.0559

GnomAD2 exomes AF: 0.0476 AC: 11897 AN: 249962 AF XY: 0.0429

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.0433

Gnomad EAS exome AF: 0.0176

Gnomad FIN exome AF: 0.0275

Gnomad NFE exome AF: 0.0300

Gnomad OTH exome AF: 0.0395

GnomAD4 exome AF: 0.0368 AC: 53724 AN: 1461382 Hom.: 1399 Cov.: 31 AF XY: 0.0360 AC XY: 26155 AN XY: 726968

African (AFR) AF: 0.153 AC: 5120 AN: 33464

American (AMR) AF: 0.105 AC: 4669 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 1099 AN: 26118

East Asian (EAS) AF: 0.0110 AC: 438 AN: 39688

South Asian (SAS) AF: 0.0283 AC: 2441 AN: 86242

European-Finnish (FIN) AF: 0.0273 AC: 1455 AN: 53290

Middle Eastern (MID) AF: 0.0496 AC: 286 AN: 5766

European-Non Finnish (NFE) AF: 0.0321 AC: 35688 AN: 1111766

Other (OTH) AF: 0.0419 AC: 2528 AN: 60378

GnomAD4 genome AF: 0.0669 AC: 10182 AN: 152232 Hom.: 555 Cov.: 32 AF XY: 0.0661 AC XY: 4918 AN XY: 74430

African (AFR) AF: 0.148 AC: 6154 AN: 41514

American (AMR) AF: 0.0683 AC: 1045 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3468

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5182

South Asian (SAS) AF: 0.0274 AC: 132 AN: 4822

European-Finnish (FIN) AF: 0.0282 AC: 300 AN: 10622

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0314 AC: 2134 AN: 68010

Other (OTH) AF: 0.0558 AC: 118 AN: 2114

Alfa AF: 0.0389 Hom.: 174

Bravo AF: 0.0741

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.69
DANN	Benign	0.79
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10422248; hg19: chr19-12911926; COSMIC: COSV56877535; COSMIC: COSV56877535;