rs56154338

Variant names:

• chr3-10213284-C-T
• rs56154338
• NM_001570.4:c.606C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001570.4(IRAK2):​c.606C>T​(p.Asp202Asp) 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
• Publications: 2 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 -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 VariationId 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 GnomAd4 at 356 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK2	NM_001570.4	MANE Select	c.606C>T	p.Asp202Asp	synonymous	Exon 5 of 13	NP_001561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK2	ENST00000256458.5	TSL:1 MANE Select	c.606C>T	p.Asp202Asp	synonymous	Exon 5 of 13	ENSP00000256458.4	O43187
	IRAK2	ENST00000971361.1		c.699C>T	p.Asp233Asp	synonymous	Exon 6 of 14	ENSP00000641420.1
	IRAK2	ENST00000873197.1		c.606C>T	p.Asp202Asp	synonymous	Exon 5 of 13	ENSP00000543256.1

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

GnomAD2 exomes AF: 0.00274 AC: 690 AN: 251476 AF XY: 0.00277

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 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

African (AFR) AF: 0.000508 AC: 17 AN: 33478

American (AMR) AF: 0.000961 AC: 43 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.00202 AC: 174 AN: 86256

European-Finnish (FIN) AF: 0.00114 AC: 61 AN: 53420

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5768

European-Non Finnish (NFE) AF: 0.00425 AC: 4727 AN: 1111984

Other (OTH) AF: 0.00308 AC: 186 AN: 60396

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

African (AFR) AF: 0.000914 AC: 38 AN: 41560

American (AMR) AF: 0.00164 AC: 25 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5168

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4820

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00385 AC: 262 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.084
DANN	Benign	0.82
PhyloP100		-2.4
Mutation Taster		=100/0	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: rs56154338; hg19: chr3-10254968; COSMIC: COSV56534030;