rs708035

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-10234479-T-A
• chr3-10234479-T-C
• chr3-10234479-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001570.4(IRAK2):​c.1293T>A​(p.Asp431Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,613,494 control chromosomes in the GnomAD database, including 375,194 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.71 (38440 hom., cov: 32)
  • Exomes 𝑓: 0.67 (336754 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.7530127E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107267 AN: 151980 Hom.: 38404 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.699

GnomAD2 exomes AF: 0.729 AC: 183045 AN: 251192 AF XY: 0.729

Gnomad AFR exome AF: 0.772

Gnomad AMR exome AF: 0.828

Gnomad ASJ exome AF: 0.687

Gnomad EAS exome AF: 0.996

Gnomad FIN exome AF: 0.623

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.692

GnomAD4 exome AF: 0.673 AC: 983485 AN: 1461396 Hom.: 336754 Cov.: 47 AF XY: 0.678 AC XY: 492837 AN XY: 726980

African (AFR) AF: 0.773 AC: 25867 AN: 33472

American (AMR) AF: 0.820 AC: 36662 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 17866 AN: 26122

East Asian (EAS) AF: 0.993 AC: 39413 AN: 39700

South Asian (SAS) AF: 0.875 AC: 75471 AN: 86256

European-Finnish (FIN) AF: 0.628 AC: 33512 AN: 53376

Middle Eastern (MID) AF: 0.714 AC: 4116 AN: 5766

European-Non Finnish (NFE) AF: 0.638 AC: 708980 AN: 1111598

Other (OTH) AF: 0.689 AC: 41598 AN: 60384

GnomAD4 genome AF: 0.706 AC: 107359 AN: 152098 Hom.: 38440 Cov.: 32 AF XY: 0.712 AC XY: 52973 AN XY: 74358

African (AFR) AF: 0.769 AC: 31931 AN: 41506

American (AMR) AF: 0.760 AC: 11613 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2389 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5137 AN: 5172

South Asian (SAS) AF: 0.890 AC: 4291 AN: 4824

European-Finnish (FIN) AF: 0.631 AC: 6667 AN: 10574

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43049 AN: 67962

Other (OTH) AF: 0.697 AC: 1474 AN: 2114

Alfa AF: 0.657 Hom.: 25167

Bravo AF: 0.717

TwinsUK AF: 0.637 AC: 2361

ALSPAC AF: 0.649 AC: 2501

ESP6500AA AF: 0.764 AC: 3367

ESP6500EA AF: 0.633 AC: 5448

ExAC AF: 0.726 AC: 88143

Asia WGS AF: 0.913 AC: 3174 AN: 3478

EpiCase AF: 0.641

EpiControl AF: 0.634

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.61
DEOGEN2	Benign	0.058	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.075	T
MetaRNN	Benign	5.8e-7	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.30
PrimateAI	Benign	0.47	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.15
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);
MPC		0.13
ClinPred		0.0014	T
GERP RS		-1.1
Varity_R		0.042
gMVP		0.15
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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; COSMIC: COSV56532113;