12-25101256-G-T

Variant names:

• chr12-25101256-G-T
• rs750930511
• NM_001366544.2:c.820G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001366544.2(IRAG2):​c.820G>T​(p.Ala274Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A274T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRAG2 NM_001366544.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21
• Publications: 1 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]

ENSG00000298872 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAG2	NM_001366544.2	MANE Select	c.820G>T	p.Ala274Ser	missense	Exon 16 of 22	NP_001353473.1	Q12912-2
	IRAG2	NM_001394803.1		c.3661G>T	p.Ala1221Ser	missense	Exon 34 of 40	NP_001381732.1
	IRAG2	NM_001204126.2		c.820G>T	p.Ala274Ser	missense	Exon 14 of 20	NP_001191055.1	Q12912-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAG2	ENST00000556887.6	TSL:5 MANE Select	c.820G>T	p.Ala274Ser	missense	Exon 16 of 22	ENSP00000451048.2	Q12912-2
	IRAG2	ENST00000354454.7	TSL:1	c.820G>T	p.Ala274Ser	missense	Exon 15 of 21	ENSP00000346442.3	Q12912-2
	IRAG2	ENST00000547044.5	TSL:1	c.820G>T	p.Ala274Ser	missense	Exon 14 of 20	ENSP00000450246.1	Q12912-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.77	T
PhyloP100		5.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.28
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.024	D
Vest4		0.56
MVP		0.49
MPC		0.78
ClinPred		0.97	D
GERP RS		4.6
gMVP		0.26
Mutation Taster		=53/47	polymorphism

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: rs750930511; hg19: chr12-25254190;