12-25092670-T-C

Position:

• chr12-25092670-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366544.2(IRAG2):​c.606+2473T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,438 control chromosomes in the GnomAD database, including 9,494 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 0.34 (9478 hom., cov: 30)
  • Exomes 𝑓: 0.22 (16 hom.)
• Consequence: IRAG2 NM_001366544.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

Genes affected

IRAG2 (HGNC:6690): (inositol 1,4,5-triphosphate receptor associated 2) The protein encode dby this gene is expressed in a developmentally regulated manner in lymphoid cell lines and tissues. The protein is localized to the cytoplasmic face of the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

CENPUP2 (HGNC:49890): (centromere protein U pseudogene 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAG2	NM_001366544.2	c.606+2473T>C		intron_variant		ENST00000556887.6	NP_001353473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAG2	ENST00000556887.6	c.606+2473T>C		intron_variant		5	NM_001366544.2	ENSP00000451048
CENPUP2	ENST00000555897.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51627 AN: 151626 Hom.: 9467 Cov.: 30

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.0956

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.217 AC: 151 AN: 696 Hom.: 16 Cov.: 0 AF XY: 0.232 AC XY: 85 AN XY: 366

Gnomad4 AFR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.0882

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.341 AC: 51675 AN: 151742 Hom.: 9478 Cov.: 30 AF XY: 0.331 AC XY: 24563 AN XY: 74128

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.0955

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.349

Alfa AF: 0.293 Hom.: 3040

Bravo AF: 0.352

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.68

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: rs7303669; hg19: chr12-25245604;