12-25092670-T-C

Variant names:

• chr12-25092670-T-C
• rs7303669
• NM_001366544.2:c.606+2473T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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)

ENSG00000298872 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IRAG2	NM_001366544.2	c.606+2473T>C		intron_variant	Intron 14 of 21	ENST00000556887.6	NP_001353473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAG2	ENST00000556887.6	c.606+2473T>C		intron_variant	Intron 14 of 21	5	NM_001366544.2	ENSP00000451048.2

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

African (AFR) AF: 0.563 AC: 18 AN: 32

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.0882 AC: 6 AN: 68

South Asian (SAS) AF: 0.375 AC: 3 AN: 8

European-Finnish (FIN) AF: 0.182 AC: 85 AN: 466

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.317 AC: 33 AN: 104

Other (OTH) AF: 0.313 AC: 5 AN: 16

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

African (AFR) AF: 0.457 AC: 18868 AN: 41298

American (AMR) AF: 0.309 AC: 4707 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1139 AN: 3470

East Asian (EAS) AF: 0.0955 AC: 494 AN: 5174

South Asian (SAS) AF: 0.286 AC: 1376 AN: 4818

European-Finnish (FIN) AF: 0.186 AC: 1956 AN: 10490

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21848 AN: 67932

Other (OTH) AF: 0.349 AC: 736 AN: 2110

Alfa AF: 0.300 Hom.: 3581

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
PhyloP100		-0.10
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: rs7303669; hg19: chr12-25245604;