chr12-25079450-A-G

Position:

• chr12-25079450-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001366544.2(IRAG2):​c.124A>G​(p.Ile42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: IRAG2 NM_001366544.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027519405).
• BP6: Variant 12-25079450-A-G is Benign according to our data. Variant chr12-25079450-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3286483.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAG2	NM_001366544.2	c.124A>G	p.Ile42Val	missense_variant	8/22	ENST00000556887.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAG2	ENST00000556887.6	c.124A>G	p.Ile42Val	missense_variant	8/22	5	NM_001366544.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460526 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726668

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74382

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.72
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.57	T;T;T;.;.;T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.028	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.33	T
Vest4		0.028, 0.031, 0.026
MVP		0.22
MPC		0.19
ClinPred		0.0095	T
GERP RS		2.4
gMVP		0.058

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs758538532; hg19: chr12-25232384; COSMIC: COSV63137648;