chr12-25079245-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001366544.2(IRAG2):ā€‹c.26A>Gā€‹(p.Glu9Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

IRAG2
NM_001366544.2 missense, splice_region

Scores

1
6
9
Splicing: ADA: 0.3965
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27125072).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IRAG2NM_001366544.2 linkuse as main transcriptc.26A>G p.Glu9Gly missense_variant, splice_region_variant 7/22 ENST00000556887.6 NP_001353473.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IRAG2ENST00000556887.6 linkuse as main transcriptc.26A>G p.Glu9Gly missense_variant, splice_region_variant 7/225 NM_001366544.2 ENSP00000451048 Q12912-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251434
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461794
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727206
show subpopulations
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:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsApr 04, 2023The c.26A>G (p.E9G) alteration is located in exon 6 (coding exon 2) of the LRMP gene. This alteration results from a A to G substitution at nucleotide position 26, causing the glutamic acid (E) at amino acid position 9 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
-0.23
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
25
DANN
Uncertain
1.0
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.73
T;T;T;.;.;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.27
T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
0.78
D;D;D;D
PrimateAI
Benign
0.41
T
PROVEAN
Pathogenic
-6.1
.;D;D;D;D;D;D
REVEL
Benign
0.13
Sift
Uncertain
0.0020
.;D;D;D;D;D;D
Sift4G
Uncertain
0.025
.;D;D;D;D;D;D
Vest4
0.27, 0.26, 0.27
MVP
0.31
MPC
0.30
ClinPred
0.82
D
GERP RS
4.8
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.40
dbscSNV1_RF
Benign
0.38
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.

Other links and lift over

dbSNP: rs769411549; hg19: chr12-25232179; API