Variant 1-234607143-GTCTC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The ENST00000366609.4(IRF2BP2):c.1754_1757del(p.Arg585ThrfsTer12) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

IRF2BP2
ENST00000366609.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.97

Variant links:

Genes affected

IRF2BP2 (HGNC:21729): (interferon regulatory factor 2 binding protein 2) This gene encodes an interferon regulatory factor-2 (IRF2) binding protein that interacts with the C-terminal transcriptional repression domain of IRF2. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

IRF2BP2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 588 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF2BP2	NM_182972.3 linkuse as main transcript	c.1754_1757del	p.Arg585ThrfsTer12	frameshift_variant	2/2	ENST00000366609.4	NP_892017.2
IRF2BP2	NM_001077397.1 linkuse as main transcript	c.1706_1709del	p.Arg569ThrfsTer12	frameshift_variant	2/2		NP_001070865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF2BP2	ENST00000366609.4 linkuse as main transcript	c.1754_1757del	p.Arg585ThrfsTer12	frameshift_variant	2/2	1	NM_182972.3	ENSP00000355568	P3	Q7Z5L9-1
IRF2BP2	ENST00000366610.7 linkuse as main transcript	c.1706_1709del	p.Arg569ThrfsTer12	frameshift_variant	2/2	1		ENSP00000355569	A1	Q7Z5L9-2
	ENST00000436039.1 linkuse as main transcript	n.142_145del		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1453958

Hom.:

AF XY:

0.00000277

AC XY:

AN XY:

721878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Varicella, severe recurrent

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Pediatric Infectious Diseases and Immunodeficiencies Unit (UPIIP)- HUVH-VHIR, Vall d'Hebron University Hospital

This variant is a deletion of 4 nucleotides in the IRF2BP2 gene located at the end of exon 2 (c.1754_1757del). This variant is very close to the end of the protein, affecting the residue 585 out of 587, causing a frameshift, and adding an additional stretch of amino acids beyond the original STOP codon (p.Arg585Thrfs*12). This makes the possible mutant protein longer than the wild type (595 vs 587 amino acids respectively). This variant was not reported in the gnomAD database. We found this variant in a patient with severe and recurrent varicella zoster virus (VZV) infection and significant VZV vaccine side-effects. The variant was inherited from his apparently asymptomatic father. The available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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