chr3-10234479-T-G

Variant names:

• chr3-10234479-T-G
• rs708035
• NM_001570.4:c.1293T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001570.4(IRAK2):​c.1293T>G​(p.Asp431Glu) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRAK2 NM_001570.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 48 publications found

Genes affected

IRAK2 (HGNC:6113): (interleukin 1 receptor associated kinase 2) IRAK2 encodes the interleukin-1 receptor-associated kinase 2, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. IRAK2 is reported to participate in the IL1-induced upregulation of NF-kappaB. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031755596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK2	NM_001570.4	c.1293T>G	p.Asp431Glu	missense_variant	Exon 11 of 13	ENST00000256458.5	NP_001561.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK2	ENST00000256458.5	c.1293T>G	p.Asp431Glu	missense_variant	Exon 11 of 13	1	NM_001570.4	ENSP00000256458.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.45
DEOGEN2	Benign	0.058	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.075	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.30
PrimateAI	Benign	0.47	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.015
MutPred		0.084		Gain of glycosylation at P433 (P = 0.1188);
MVP		0.44
MPC		0.13
ClinPred		0.092	T
GERP RS		-1.1
Varity_R		0.042
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs708035; hg19: chr3-10276163;