3-10213284-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001570.4(IRAK2):c.606C>T(p.Asp202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,614,126 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0036 (12 hom.)
• Consequence: IRAK2 NM_001570.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.43

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-10213284-C-T is Benign according to our data. Variant chr3-10213284-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.43 with no splicing effect.
• BS2: High AC in GnomAd at 356 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK2	NM_001570.4	c.606C>T	p.Asp202=	synonymous_variant	5/13	ENST00000256458.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK2	ENST00000256458.5	c.606C>T	p.Asp202=	synonymous_variant	5/13	1	NM_001570.4	P1

Frequencies

GnomAD3 genomes AF: 0.00234 AC: 356 AN: 152146 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00274 AC: 690 AN: 251476 Hom.: 2 AF XY: 0.00277 AC XY: 376 AN XY: 135916

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.000598

Gnomad SAS exome AF: 0.00216

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00466

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00359 AC: 5249 AN: 1461862 Hom.: 12 Cov.: 32 AF XY: 0.00353 AC XY: 2569 AN XY: 727234

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000961

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00202

Gnomad4 FIN exome AF: 0.00114

Gnomad4 NFE exome AF: 0.00425

Gnomad4 OTH exome AF: 0.00308

GnomAD4 genome AF: 0.00234 AC: 356 AN: 152264 Hom.: 0 Cov.: 31 AF XY: 0.00227 AC XY: 169 AN XY: 74430

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00385

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00296 Hom.: 0

Bravo AF: 0.00224

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00474

EpiControl AF: 0.00427

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

Feb 01, 2023

IRAK2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.084
Dann	Benign	0.82

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: rs56154338; hg19: chr3-10254968; COSMIC: COSV56534030;