Genetic Variant IRAG2:p.Leu141Phe (chr12-25089661-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366544.2(IRAG2):c.421C>T(p.Leu141Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

IRAG2
NM_001366544.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.788

Publications

39 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:

ENSG00000298872 (HGNC:):

ENSG00000298872 links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.032897413).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
IRAG2	NM_001366544.2	MANE Select	c.421C>T	p.Leu141Phe	missense	Exon 12 of 22	NP_001353473.1	Q12912-2
IRAG2	NM_001394803.1		c.3262C>T	p.Leu1088Phe	missense	Exon 30 of 40	NP_001381732.1
IRAG2	NM_001204126.2		c.421C>T	p.Leu141Phe	missense	Exon 10 of 20	NP_001191055.1	Q12912-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRAG2	ENST00000556887.6	TSL:5 MANE Select	c.421C>T	p.Leu141Phe	missense	Exon 12 of 22	ENSP00000451048.2	Q12912-2
IRAG2	ENST00000354454.7	TSL:1	c.421C>T	p.Leu141Phe	missense	Exon 11 of 21	ENSP00000346442.3	Q12912-2
IRAG2	ENST00000547044.5	TSL:1	c.421C>T	p.Leu141Phe	missense	Exon 10 of 20	ENSP00000450246.1	Q12912-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152058

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74244

African (AFR)

AF:

0.00

AC:

AN:

41368

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.76

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.14

M_CAP

Benign

0.0030

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

PhyloP100

0.79

PrimateAI

Benign

0.48

PROVEAN

Benign

2.2

REVEL

Benign

0.052

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.038

MVP

0.048

MPC

0.25

ClinPred

0.075

GERP RS

4.3

PromoterAI

-0.0094

Neutral

(source)

gMVP

0.056

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over