rs553797728

Variant names:

• chr12-25090096-T-C
• rs553797728
• NM_001366544.2:c.505T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-25090096-T-C
• chr12-25090096-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366544.2(IRAG2):​c.505T>C​(p.Trp169Arg) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W169G) 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: 0.428
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20594358).

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.505T>C	p.Trp169Arg	missense	Exon 14 of 22	NP_001353473.1	Q12912-2
	IRAG2	NM_001394803.1		c.3346T>C	p.Trp1116Arg	missense	Exon 32 of 40	NP_001381732.1
	IRAG2	NM_001204126.2		c.505T>C	p.Trp169Arg	missense	Exon 12 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.505T>C	p.Trp169Arg	missense	Exon 14 of 22	ENSP00000451048.2	Q12912-2
	IRAG2	ENST00000354454.7	TSL:1	c.505T>C	p.Trp169Arg	missense	Exon 13 of 21	ENSP00000346442.3	Q12912-2
	IRAG2	ENST00000547044.5	TSL:1	c.505T>C	p.Trp169Arg	missense	Exon 12 of 20	ENSP00000450246.1	Q12912-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.89
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.43
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.11
Sift	Benign	0.94	T
Sift4G	Benign	0.094	T
Vest4		0.26
MVP		0.16
MPC		1.0
ClinPred		0.47	T
GERP RS		3.4
PromoterAI		0.010	Neutral
gMVP		0.19
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs553797728; hg19: chr12-25243030;