1-234609354-G-C

Variant names:

• chr1-234609354-G-C
• rs771111724
• NM_182972.3:c.141C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182972.3(IRF2BP2):​c.141C>G​(p.Asp47Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: IRF2BP2 NM_182972.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

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]

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

ENSG00000228830 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2951313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3	c.141C>G	p.Asp47Glu	missense_variant	Exon 1 of 2	ENST00000366609.4	NP_892017.2
IRF2BP2	NM_001077397.1	c.141C>G	p.Asp47Glu	missense_variant	Exon 1 of 2		NP_001070865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF2BP2	ENST00000366609.4	c.141C>G	p.Asp47Glu	missense_variant	Exon 1 of 2	1	NM_182972.3	ENSP00000355568.3
IRF2BP2	ENST00000366610.8	c.141C>G	p.Asp47Glu	missense_variant	Exon 1 of 2	1		ENSP00000355569.3
LINC00184	ENST00000796406.1	n.60G>C		non_coding_transcript_exon_variant	Exon 1 of 4
ENSG00000228830	ENST00000436039.1	n.631-67G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 10, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with IRF2BP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 47 of the IRF2BP2 protein (p.Asp47Glu). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		2.3
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.017	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.36	B;B
Vest4		0.50
MutPred		0.56		Loss of stability (P = 0.134);Loss of stability (P = 0.134);
MVP		0.67
MPC		2.3
ClinPred		0.90	D
GERP RS		2.6
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.53
gMVP		0.69
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs771111724; hg19: chr1-234745100;