rs1979522

Positions:

• chr12-25090959-C-T

Variant summary

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

The NM_001366544.2(IRAG2):​c.606+762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 413,390 control chromosomes in the GnomAD database, including 1,790 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 0.082 (535 hom., cov: 32)
  • Exomes 𝑓: 0.091 (1255 hom.)
• Consequence: IRAG2 NM_001366544.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

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]

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 (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAG2	NM_001366544.2	c.606+762C>T		intron_variant		ENST00000556887.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAG2	ENST00000556887.6	c.606+762C>T		intron_variant		5	NM_001366544.2

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12521 AN: 152002 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.00731

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0912

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0824

GnomAD4 exome AF: 0.0907 AC: 23686 AN: 261272 Hom.: 1255 Cov.: 0 AF XY: 0.0948 AC XY: 14037 AN XY: 148112

Gnomad4 AFR exome AF: 0.0762

Gnomad4 AMR exome AF: 0.0581

Gnomad4 ASJ exome AF: 0.0585

Gnomad4 EAS exome AF: 0.00648

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0888

Gnomad4 NFE exome AF: 0.0900

Gnomad4 OTH exome AF: 0.0840

GnomAD4 genome AF: 0.0824 AC: 12533 AN: 152118 Hom.: 535 Cov.: 32 AF XY: 0.0796 AC XY: 5922 AN XY: 74372

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.0575

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.00733

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0912

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.0820

Alfa AF: 0.0875 Hom.: 834

Bravo AF: 0.0789

Asia WGS AF: 0.0740 AC: 259 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	5.3
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs1979522; hg19: chr12-25243893;