rs12151144

chr19-12801582-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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/exons	MANE	UniProt
PRDX2	NM_005809.6	c.-10+158T>G		intron_variant		ENST00000301522.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDX2	ENST00000301522.3	c.-10+158T>G		intron_variant		1	NM_005809.6	P1
	ENST00000585496.1	n.201-172A>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.0914

Gnomad4 EAS AF: 0.0611

Gnomad4 SAS AF: 0.0946

Gnomad4 FIN AF: 0.0823

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.177

Alfa AF: 0.130 Hom.: 1317

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

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: rs12151144; hg19: chr19-12912396;