Genetic Variant IRF2BP2:p.Pro67Thr (chr1-234609296-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182972.3(IRF2BP2):c.199C>A(p.Pro67Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P67S) has been classified 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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.95

Publications

0 publications found

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:

LINC00184 (HGNC:37192): (long intergenic non-protein coding RNA 184)

LINC00184 links:

ENSG00000228830 (HGNC:):

ENSG00000228830 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12803471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3 link	c.199C>A	p.Pro67Thr	missense_variant	Exon 1 of 2	ENST00000366609.4	NP_892017.2	Q7Z5L9-1
IRF2BP2	NM_001077397.1 link	c.199C>A	p.Pro67Thr	missense_variant	Exon 1 of 2		NP_001070865.1	Q7Z5L9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IRF2BP2	ENST00000366609.4 link	c.199C>A	p.Pro67Thr	missense_variant	Exon 1 of 2	1	NM_182972.3	ENSP00000355568.3	Q7Z5L9-1
IRF2BP2	ENST00000366610.8 link	c.199C>A	p.Pro67Thr	missense_variant	Exon 1 of 2	1		ENSP00000355569.3	Q7Z5L9-2
LINC00184	ENST00000796406.1 link	n.2G>T		non_coding_transcript_exon_variant	Exon 1 of 4
ENSG00000228830	ENST00000436039.1 link	n.631-125G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1327104

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654460

African (AFR)

AF:

0.00

AC:

AN:

26864

American (AMR)

AF:

0.00

AC:

AN:

27176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22946

East Asian (EAS)

AF:

0.00

AC:

AN:

28570

South Asian (SAS)

AF:

0.00

AC:

AN:

72584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4086

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1044992

Other (OTH)

AF:

0.00

AC:

AN:

54438

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PhyloP100

3.9

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.066

Sift

Benign

0.032

D;T

Sift4G

Benign

0.084

T;T

Polyphen

0.56

P;B

Vest4

0.15

MutPred

0.17

Gain of phosphorylation at P67 (P = 0.0392);Gain of phosphorylation at P67 (P = 0.0392);

MVP

0.28

MPC

1.3

ClinPred

0.40

GERP RS

2.7

PromoterAI

-0.066

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.081

gMVP

0.20

Mutation Taster

=71/29

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over