chr12-25107981-A-G

Position:

• chr12-25107981-A-G

Variant summary

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

The NM_001366544.2(IRAG2):​c.1421A>G​(p.Gln474Arg) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRAG2 NM_001366544.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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]

DNAI7 (HGNC:):

ACMG classification

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=0.0647068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAG2	NM_001366544.2	c.1421A>G	p.Gln474Arg	missense_variant	22/22	ENST00000556887.6	NP_001353473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAG2	ENST00000556887.6	c.1421A>G	p.Gln474Arg	missense_variant	22/22	5	NM_001366544.2	ENSP00000451048

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2022

The c.1421A>G (p.Q474R) alteration is located in exon 21 (coding exon 17) of the LRMP gene. This alteration results from a A to G substitution at nucleotide position 1421, causing the glutamine (Q) at amino acid position 474 to be replaced by an arginine (R). 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	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.96
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.57	T;.;T;.;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.065	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.92	.;N;N;N;N
REVEL	Benign	0.037
Sift	Benign	0.22	.;T;T;T;T
Sift4G	Benign	0.49	.;T;T;T;T
Vest4		0.088, 0.059, 0.090, 0.082
MVP		0.14
MPC		0.27
ClinPred		0.046	T
GERP RS		3.1
gMVP		0.074

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-25260915;