rs10413408

Variant names:

• chr19-12800165-G-T
• rs10413408
• NM_005809.6:c.380+12C>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.380+12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,612,648 control chromosomes in the GnomAD database, including 2,132 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 0.070 (647 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1485 hom.)
• Consequence: PRDX2 NM_005809.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 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.380+12C>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.380+12C>A		intron	N/A	ENSP00000301522.2	P32119-1
	PRDX2	ENST00000466174.5	TSL:1	n.1067C>A		non_coding_transcript_exon	Exon 3 of 4
	PRDX2	ENST00000866180.1		c.380+12C>A		intron	N/A	ENSP00000536239.1

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10678 AN: 152100 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0578

GnomAD2 exomes AF: 0.0486 AC: 12167 AN: 250606 AF XY: 0.0435

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.0432

Gnomad EAS exome AF: 0.0175

Gnomad FIN exome AF: 0.0275

Gnomad NFE exome AF: 0.0301

Gnomad OTH exome AF: 0.0399

GnomAD4 exome AF: 0.0371 AC: 54245 AN: 1460430 Hom.: 1485 Cov.: 32 AF XY: 0.0363 AC XY: 26383 AN XY: 726348

African (AFR) AF: 0.165 AC: 5507 AN: 33466

American (AMR) AF: 0.106 AC: 4712 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 1098 AN: 26100

East Asian (EAS) AF: 0.0110 AC: 436 AN: 39668

South Asian (SAS) AF: 0.0283 AC: 2442 AN: 86168

European-Finnish (FIN) AF: 0.0274 AC: 1453 AN: 53118

Middle Eastern (MID) AF: 0.0494 AC: 284 AN: 5744

European-Non Finnish (NFE) AF: 0.0322 AC: 35741 AN: 1111194

Other (OTH) AF: 0.0426 AC: 2572 AN: 60328

GnomAD4 genome AF: 0.0704 AC: 10709 AN: 152218 Hom.: 647 Cov.: 32 AF XY: 0.0695 AC XY: 5174 AN XY: 74412

African (AFR) AF: 0.160 AC: 6635 AN: 41500

American (AMR) AF: 0.0708 AC: 1082 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3470

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5180

South Asian (SAS) AF: 0.0274 AC: 132 AN: 4824

European-Finnish (FIN) AF: 0.0281 AC: 298 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0315 AC: 2141 AN: 68014

Other (OTH) AF: 0.0577 AC: 122 AN: 2114

Alfa AF: 0.0520 Hom.: 155

Bravo AF: 0.0786

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.65
PhyloP100		-1.7
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: rs10413408; hg19: chr19-12910979;