Genetic Variant NM_182972.3:c.1756_1757delGA (chr1-234607143-GTC-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PVS1_ModerateBS2

The NM_182972.3(IRF2BP2):c.1756_1757delGA(p.Asp586LeufsTer15) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,453,962 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

IRF2BP2
NM_182972.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.97

Publications

1 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 Gene-Disease associations (from GenCC):

immunodeficiency, common variable, 14
Inheritance: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

IRF2BP2 links:

ENSG00000228830 (HGNC:):

ENSG00000228830 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00454 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BS2

High AC in GnomAdExome4 at 22 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF2BP2	NM_182972.3 link	c.1756_1757delGA	p.Asp586LeufsTer15	frameshift_variant	Exon 2 of 2	ENST00000366609.4	NP_892017.2	Q7Z5L9-1
IRF2BP2	NM_001077397.1 link	c.1708_1709delGA	p.Asp570LeufsTer15	frameshift_variant	Exon 2 of 2		NP_001070865.1	Q7Z5L9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IRF2BP2	ENST00000366609.4 link	c.1756_1757delGA	p.Asp586LeufsTer15	frameshift_variant	Exon 2 of 2	1	NM_182972.3	ENSP00000355568.3	Q7Z5L9-1
IRF2BP2	ENST00000366610.8 link	c.1708_1709delGA	p.Asp570LeufsTer15	frameshift_variant	Exon 2 of 2	1		ENSP00000355569.3	Q7Z5L9-2
ENSG00000228830	ENST00000436039.1 link	n.144_145delCT		non_coding_transcript_exon_variant	Exon 1 of 2	3
IRF2BP2	ENST00000491430.1 link	n.86_87delGA		downstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000201

AC:

AN:

249228

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1453962

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

721882

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33200

American (AMR)

AF:

0.0000226

AC:

AN:

44294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25940

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39516

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86110

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.0000145

AC:

AN:

1106022

Other (OTH)

AF:

0.0000333

AC:

AN:

59978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

8.0

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

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NM_182972.3:c.1756_1757delGA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over