3-10164953-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001570.4(IRAK2):c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000997 in 1,607,188 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00088 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (13 hom.)
• Consequence: IRAK2 NM_001570.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.975

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-10164953-C-T is Benign according to our data. Variant chr3-10164953-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK2	NM_001570.4	c.-2C>T		5_prime_UTR_variant	1/13	ENST00000256458.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK2	ENST00000256458.5	c.-2C>T		5_prime_UTR_variant	1/13	1	NM_001570.4	P1

Frequencies

GnomAD3 genomes AF: 0.000880 AC: 134 AN: 152224 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00868

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00175 AC: 424 AN: 241628 Hom.: 6 AF XY: 0.00204 AC XY: 268 AN XY: 131490

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.000177

Gnomad ASJ exome AF: 0.00663

Gnomad EAS exome AF: 0.0000560

Gnomad SAS exome AF: 0.00890

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000692

Gnomad OTH exome AF: 0.00136

GnomAD4 exome AF: 0.00101 AC: 1468 AN: 1454846 Hom.: 13 Cov.: 31 AF XY: 0.00123 AC XY: 892 AN XY: 723708

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.000271

Gnomad4 ASJ exome AF: 0.00605

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.00834

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000414

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.000880 AC: 134 AN: 152342 Hom.: 1 Cov.: 32 AF XY: 0.00107 AC XY: 80 AN XY: 74508

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00869

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000617

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.000710

Asia WGS AF: 0.00433 AC: 15 AN: 3478

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, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	13
Dann	Benign	0.85

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: rs146076327; hg19: chr3-10206637;