Genetic Variant NM_001366544.2:c.606+2473T>C (chr12-25092670-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.105

Publications

3 publications found

Variant links:

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]

IRAG2 links:

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

CENPUP2 links:

ENSG00000298872 (HGNC:):

ENSG00000298872 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366544.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IRAG2	NM_001366544.2	MANE Select	c.606+2473T>C	intron	N/A	NP_001353473.1
IRAG2	NM_001394803.1		c.3447+2473T>C	intron	N/A	NP_001381732.1
IRAG2	NM_001204126.2		c.606+2473T>C	intron	N/A	NP_001191055.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IRAG2	ENST00000556887.6	TSL:5 MANE Select	c.606+2473T>C	intron	N/A	ENSP00000451048.2
IRAG2	ENST00000354454.7	TSL:1	c.606+2473T>C	intron	N/A	ENSP00000346442.3
IRAG2	ENST00000547044.5	TSL:1	c.606+2473T>C	intron	N/A	ENSP00000450246.1

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51627

AN:

151626

Hom.:

9467

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.232

AC XY:

AN XY:

366

show subpopulations

African (AFR)

AF:

0.563

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.0882

AC:

AN:

South Asian (SAS)

AF:

0.375

AC:

AN:

European-Finnish (FIN)

AF:

0.182

AC:

AN:

466

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.317

AC:

AN:

104

Other (OTH)

AF:

0.313

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.341

AC:

51675

AN:

151742

Hom.:

9478

Cov.:

AF XY:

0.331

AC XY:

24563

AN XY:

74128

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1624

3249

4873

6498

8122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.3

(source)

DANN

Benign

0.68

PhyloP100

-0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over