19-12800471-T-C

Variant names:

• chr19-12800471-T-C
• rs10427027
• NM_005809.6:c.258-172A>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.258-172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 909,506 control chromosomes in the GnomAD database, including 12,083 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 (5584 hom., cov: 31)
  • Exomes 𝑓: 0.11 (6499 hom.)
• Consequence: PRDX2 NM_005809.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 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.258-172A>G		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.258-172A>G		intron	N/A	ENSP00000301522.2	P32119-1
	PRDX2	ENST00000466174.5	TSL:1	n.761A>G		non_coding_transcript_exon	Exon 3 of 4
	PRDX2	ENST00000866180.1		c.258-172A>G		intron	N/A	ENSP00000536239.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32108 AN: 151930 Hom.: 5561 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.113 AC: 85968 AN: 757458 Hom.: 6499 Cov.: 10 AF XY: 0.112 AC XY: 42952 AN XY: 382220

African (AFR) AF: 0.485 AC: 8733 AN: 18008

American (AMR) AF: 0.174 AC: 3223 AN: 18482

Ashkenazi Jewish (ASJ) AF: 0.0933 AC: 1443 AN: 15474

East Asian (EAS) AF: 0.0753 AC: 2442 AN: 32450

South Asian (SAS) AF: 0.102 AC: 5301 AN: 51928

European-Finnish (FIN) AF: 0.0788 AC: 2983 AN: 37872

Middle Eastern (MID) AF: 0.117 AC: 377 AN: 3216

European-Non Finnish (NFE) AF: 0.105 AC: 56938 AN: 544218

Other (OTH) AF: 0.126 AC: 4528 AN: 35810

GnomAD4 genome AF: 0.212 AC: 32174 AN: 152048 Hom.: 5584 Cov.: 31 AF XY: 0.206 AC XY: 15352 AN XY: 74354

African (AFR) AF: 0.476 AC: 19708 AN: 41432

American (AMR) AF: 0.176 AC: 2690 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 317 AN: 3472

East Asian (EAS) AF: 0.0604 AC: 312 AN: 5162

South Asian (SAS) AF: 0.0939 AC: 453 AN: 4824

European-Finnish (FIN) AF: 0.0821 AC: 871 AN: 10608

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

European-Non Finnish (NFE) AF: 0.107 AC: 7293 AN: 67972

Other (OTH) AF: 0.174 AC: 366 AN: 2100

Alfa AF: 0.196 Hom.: 1928

Bravo AF: 0.230

Asia WGS AF: 0.107 AC: 373 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	1.0
DANN	Benign	0.55
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10427027; hg19: chr19-12911285;