rs11465886

Positions:

• chr3-10209099-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001570.4(IRAK2):​c.425-490A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 151,954 control chromosomes in the GnomAD database, including 1,002 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.078 (1002 hom., cov: 31)
• Consequence: IRAK2 NM_001570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK2	NM_001570.4	c.425-490A>G		intron_variant		ENST00000256458.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK2	ENST00000256458.5	c.425-490A>G		intron_variant		1	NM_001570.4	P1

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11785 AN: 151836 Hom.: 993 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0780

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.00567

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0656

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0778 AC: 11828 AN: 151954 Hom.: 1002 Cov.: 31 AF XY: 0.0756 AC XY: 5615 AN XY: 74256

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.0406

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.0782

Gnomad4 SAS AF: 0.0599

Gnomad4 FIN AF: 0.00567

Gnomad4 NFE AF: 0.0182

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.0291 Hom.: 234

Bravo AF: 0.0861

Asia WGS AF: 0.0770 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs11465886; hg19: chr3-10250783;