rs12151144

Variant names:

• chr19-12801582-A-C
• rs12151144
• NM_005809.6:c.-10+158T>G

Variant summary

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

The NM_005809.6(PRDX2):​c.-10+158T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,250 control chromosomes in the GnomAD database, including 5,626 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 0.21 (5626 hom., cov: 33)
• Consequence: PRDX2 NM_005809.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX2	NM_005809.6	c.-10+158T>G		intron_variant	Intron 1 of 5	ENST00000301522.3	NP_005800.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX2	ENST00000301522.3	c.-10+158T>G		intron_variant	Intron 1 of 5	1	NM_005809.6	ENSP00000301522.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32249 AN: 152132 Hom.: 5603 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.0941

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.212 AC: 32315 AN: 152250 Hom.: 5626 Cov.: 33 AF XY: 0.207 AC XY: 15429 AN XY: 74458

African (AFR) AF: 0.477 AC: 19789 AN: 41526

American (AMR) AF: 0.178 AC: 2723 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3470

East Asian (EAS) AF: 0.0611 AC: 316 AN: 5176

South Asian (SAS) AF: 0.0946 AC: 457 AN: 4830

European-Finnish (FIN) AF: 0.0823 AC: 875 AN: 10628

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7298 AN: 67998

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.135 Hom.: 1599

Bravo AF: 0.230

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.96
DANN	Benign	0.22
PhyloP100		-1.4
PromoterAI		-0.14	Neutral
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: rs12151144; hg19: chr19-12912396;