1-234609314-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_182972.3(IRF2BP2):c.181C>T(p.Arg61Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000464 in 1,507,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

IRF2BP2
NM_182972.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.740

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: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

BS2

High AC in GnomAdExome4 at 6 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3 link	c.181C>T	p.Arg61Trp	missense_variant	Exon 1 of 2	ENST00000366609.4	NP_892017.2	Q7Z5L9-1
IRF2BP2	NM_001077397.1 link	c.181C>T	p.Arg61Trp	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.181C>T	p.Arg61Trp	missense_variant	Exon 1 of 2	1	NM_182972.3	ENSP00000355568.3	Q7Z5L9-1
IRF2BP2	ENST00000366610.8 link	c.181C>T	p.Arg61Trp	missense_variant	Exon 1 of 2	1		ENSP00000355569.3	Q7Z5L9-2
LINC00184	ENST00000796406.1 link	n.20G>A		non_coding_transcript_exon_variant	Exon 1 of 4
ENSG00000228830	ENST00000436039.1 link	n.631-107G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000851

AC:

AN:

117470

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000222

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000442

AC:

AN:

1356300

Hom.:

Cov.:

AF XY:

0.00000298

AC XY:

AN XY:

670346

show subpopulations

African (AFR)

AF:

0.0000364

AC:

AN:

27472

American (AMR)

AF:

0.00

AC:

AN:

31014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23630

East Asian (EAS)

AF:

0.00

AC:

AN:

29836

South Asian (SAS)

AF:

0.00

AC:

AN:

75510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4282

European-Non Finnish (NFE)

AF:

0.00000377

AC:

AN:

1061656

Other (OTH)

AF:

0.0000179

AC:

AN:

55768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151414

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73964

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41336

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67766

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Mar 27, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 61 of the IRF2BP2 protein (p.Arg61Trp). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with IRF2BP2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.038

FATHMM_MKL

Benign

0.62

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Pathogenic

0.56

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.4

L;L

PhyloP100

0.74

PrimateAI

Pathogenic

0.96

PROVEAN

Pathogenic

-6.2

D;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.53

MutPred

0.50

Gain of catalytic residue at L59 (P = 0.0044);Gain of catalytic residue at L59 (P = 0.0044);

MVP

0.63

MPC

2.4

ClinPred

0.99

GERP RS

2.7

PromoterAI

-0.096

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.84

gMVP

0.64

Mutation Taster

=48/52

disease causing

(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.

1-234609314-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over