Genetic Variant NM_005809.6:c.380+12C>A (chr19-12800165-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Variant links:

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 links:

ENSG00000267062 (HGNC:):

ENSG00000267062 links:

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]

HOOK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX2	NM_005809.6 link	c.380+12C>A		intron_variant	Intron 4 of 5	ENST00000301522.3	NP_005800.3	P32119-1V9HW12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX2	ENST00000301522.3 link	c.380+12C>A		intron_variant	Intron 4 of 5	1	NM_005809.6	ENSP00000301522.2		P32119-1

Frequencies

GnomAD3 genomes

AF:

0.0702

AC:

10678

AN:

152100

Hom.:

643

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0486

AC:

12167

AN:

250606

Hom.:

513

AF XY:

0.0435

AC XY:

5898

AN XY:

135518

show subpopulations

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 SAS exome

AF:

0.0269

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.:

AF XY:

0.0363

AC XY:

26383

AN XY:

726348

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.0421

Gnomad4 EAS exome

AF:

0.0110

Gnomad4 SAS exome

AF:

0.0283

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0322

Gnomad4 OTH exome

AF:

0.0426

GnomAD4 genome

AF:

0.0704

AC:

10709

AN:

152218

Hom.:

647

Cov.:

AF XY:

0.0695

AC XY:

5174

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.0708

Gnomad4 ASJ

AF:

0.0427

Gnomad4 EAS

AF:

0.0172

Gnomad4 SAS

AF:

0.0274

Gnomad4 FIN

AF:

0.0281

Gnomad4 NFE

AF:

0.0315

Gnomad4 OTH

AF:

0.0577

Alfa

AF:

0.0503

Hom.:

122

Bravo

AF:

0.0786

Asia WGS

AF:

0.0320

AC:

110

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.13

DANN

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over