3-10178004-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001570.4(IRAK2):c.261C>T(p.Ala87=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 1,609,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (0 hom.)
• Consequence: IRAK2 NM_001570.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.625

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 3-10178004-C-T is Benign according to our data. Variant chr3-10178004-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653515.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.625 with no splicing effect.
• BS2: High AC in GnomAd at 112 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK2	NM_001570.4	c.261C>T	p.Ala87=	synonymous_variant	2/13	ENST00000256458.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK2	ENST00000256458.5	c.261C>T	p.Ala87=	synonymous_variant	2/13	1	NM_001570.4	P1

Frequencies

GnomAD3 genomes AF: 0.000736 AC: 112 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000734 AC: 181 AN: 246478 Hom.: 0 AF XY: 0.000706 AC XY: 94 AN XY: 133220

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00438

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00459

Gnomad NFE exome AF: 0.000369

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000467 AC: 681 AN: 1457322 Hom.: 0 Cov.: 36 AF XY: 0.000486 AC XY: 352 AN XY: 724802

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00450

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00368

Gnomad4 NFE exome AF: 0.000315

Gnomad4 OTH exome AF: 0.000332

GnomAD4 genome AF: 0.000736 AC: 112 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.00112 AC XY: 83 AN XY: 74348

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000660 Hom.: 0

Bravo AF: 0.000317

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

IRAK2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	8.0
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs141395070; hg19: chr3-10219688; COSMIC: COSV56530402;