chr19-12800471-T-A

Variant names:

• chr19-12800471-T-A
• rs10427027
• ENST00000466174.5:n.761A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000466174.5(PRDX2):​n.761A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 758,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: PRDX2 ENST00000466174.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDX2	NM_005809.6	c.258-172A>T		intron_variant	Intron 3 of 5	ENST00000301522.3	NP_005800.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDX2	ENST00000301522.3	c.258-172A>T		intron_variant	Intron 3 of 5	1	NM_005809.6	ENSP00000301522.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000132 AC: 1 AN: 758200 Hom.: 0 Cov.: 10 AF XY: 0.00000261 AC XY: 1 AN XY: 382604

African (AFR) AF: 0.00 AC: 0 AN: 18044

American (AMR) AF: 0.00 AC: 0 AN: 18502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15484

East Asian (EAS) AF: 0.00 AC: 0 AN: 32466

South Asian (SAS) AF: 0.00 AC: 0 AN: 51958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3220

European-Non Finnish (NFE) AF: 0.00000184 AC: 1 AN: 544796

Other (OTH) AF: 0.00 AC: 0 AN: 35836

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.61
DANN	Benign	0.61
PhyloP100		-3.2

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: rs10427027; hg19: chr19-12911285;