Variant 12-25079656-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366544.2(IRAG2):c.137A>G(p.Asp46Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000901 in 1,443,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

IRAG2
NM_001366544.2 missense, splice_region

Scores

Splicing: ADA: 0.00001648

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

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:

IRAG2 (HGNC:):

IRAG2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06542966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAG2	NM_001366544.2 linkuse as main transcript	c.137A>G	p.Asp46Gly	missense_variant, splice_region_variant	9/22	ENST00000556887.6	NP_001353473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAG2	ENST00000556887.6 linkuse as main transcript	c.137A>G	p.Asp46Gly	missense_variant, splice_region_variant	9/22	5	NM_001366544.2	ENSP00000451048.2		Q12912-2A0A0G2JL87

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251210

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000901

AC:

AN:

1443392

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

719368

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000291

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.137A>G (p.D46G) alteration is located in exon 8 (coding exon 4) of the LRMP gene. This alteration results from a A to G substitution at nucleotide position 137, causing the aspartic acid (D) at amino acid position 46 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.82

T;T;T;.;.;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.065

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.7

.;D;D;D;D;D;D

REVEL

Benign

0.051

Sift

Uncertain

0.0050

.;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

.;D;D;T;T;D;T

Vest4

0.42, 0.37, 0.41

MVP

0.17

MPC

0.95

ClinPred

0.31

GERP RS

1.9

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over