Genetic Variant IRAK2:c.1210-38C>T (chr3-10226333-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001570.4(IRAK2):c.1210-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,559,626 control chromosomes in the GnomAD database, including 36,996 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 0.23 ( 5020 hom., cov: 31)

Exomes 𝑓: 0.18 ( 31976 hom. )

Consequence

IRAK2
NM_001570.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.586

Publications

9 publications found

Variant links:

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]

IRAK2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

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.1210-38C>T		intron	N/A	NP_001561.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IRAK2	ENST00000256458.5	TSL:1 MANE Select	c.1210-38C>T	intron	N/A	ENSP00000256458.4
IRAK2	ENST00000971361.1		c.1303-38C>T	intron	N/A	ENSP00000641420.1
IRAK2	ENST00000873197.1		c.1210-38C>T	intron	N/A	ENSP00000543256.1

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34488

AN:

151906

Hom.:

5013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.226

GnomAD2 exomes

AF:

0.249

AC:

61442

AN:

246826

AF XY:

0.248

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.183

AC:

257278

AN:

1407600

Hom.:

31976

Cov.:

AF XY:

0.188

AC XY:

132154

AN XY:

702230

show subpopulations

African (AFR)

AF:

0.321

AC:

10378

AN:

32312

American (AMR)

AF:

0.288

AC:

12705

AN:

44166

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

5149

AN:

25704

East Asian (EAS)

AF:

0.651

AC:

25530

AN:

39230

South Asian (SAS)

AF:

0.387

AC:

32769

AN:

84714

European-Finnish (FIN)

AF:

0.160

AC:

8470

AN:

52778

Middle Eastern (MID)

AF:

0.250

AC:

1336

AN:

5346

European-Non Finnish (NFE)

AF:

0.140

AC:

148709

AN:

1064882

Other (OTH)

AF:

0.209

AC:

12232

AN:

58468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8971

17942

26913

35884

44855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5848

11696

17544

23392

29240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.227

AC:

34516

AN:

152026

Hom.:

5020

Cov.:

AF XY:

0.235

AC XY:

17439

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.311

AC:

12869

AN:

41424

American (AMR)

AF:

0.239

AC:

3651

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

747

AN:

3470

East Asian (EAS)

AF:

0.638

AC:

3296

AN:

5166

South Asian (SAS)

AF:

0.405

AC:

1949

AN:

4814

European-Finnish (FIN)

AF:

0.163

AC:

1726

AN:

10578

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9509

AN:

67996

Other (OTH)

AF:

0.226

AC:

476

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1262

2523

3785

5046

6308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.162

Hom.:

1862

Bravo

AF:

0.236

Asia WGS

AF:

0.492

AC:

1706

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.24

(source)

DANN

Benign

0.65

PhyloP100

-0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over