1-234609365-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182972.3(IRF2BP2):​c.130G>A​(p.Glu44Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IRF2BP2
NM_182972.3 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.47
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IRF2BP2NM_182972.3 linkc.130G>A p.Glu44Lys missense_variant Exon 1 of 2 ENST00000366609.4 NP_892017.2 Q7Z5L9-1
IRF2BP2NM_001077397.1 linkc.130G>A p.Glu44Lys missense_variant Exon 1 of 2 NP_001070865.1 Q7Z5L9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IRF2BP2ENST00000366609.4 linkc.130G>A p.Glu44Lys missense_variant Exon 1 of 2 1 NM_182972.3 ENSP00000355568.3 Q7Z5L9-1
IRF2BP2ENST00000366610.7 linkc.130G>A p.Glu44Lys missense_variant Exon 1 of 2 1 ENSP00000355569.3 Q7Z5L9-2
ENSG00000228830ENST00000436039.1 linkn.631-56C>T intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1400204
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
694872
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Sep 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 44 of the IRF2BP2 protein (p.Glu44Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IRF2BP2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, 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
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
.;T
Eigen
Benign
0.13
Eigen_PC
Benign
-0.045
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Pathogenic
0.61
D
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.5
L;L
PrimateAI
Pathogenic
0.93
D
PROVEAN
Uncertain
-3.2
D;D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;D
Vest4
0.59
MutPred
0.59
Gain of ubiquitination at E44 (P = 0.0203);Gain of ubiquitination at E44 (P = 0.0203);
MVP
0.63
MPC
2.4
ClinPred
0.99
D
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.69
gMVP
0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-234745111; API