2-213054565-G-T

Variant names:

• chr2-213054565-G-T
• rs9288462
• NM_001387220.1:c.406+2268C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387220.1(IKZF2):​c.406+2268C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,012 control chromosomes in the GnomAD database, including 21,927 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (21927 hom., cov: 33)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 3 publications found

Genes affected

IKZF2 (HGNC:13177): (IKAROS family zinc finger 2) This gene encodes a member of the Ikaros family of zinc-finger proteins. Three members of this protein family (Ikaros, Aiolos and Helios) are hematopoietic-specific transcription factors involved in the regulation of lymphocyte development. This protein forms homo- or hetero-dimers with other Ikaros family members, and is thought to function predominantly in early hematopoietic development. Multiple transcript variants encoding different isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

IKZF2 Gene-Disease associations (from GenCC):

• HELIOS deficiency

  Inheritance: SD, AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• hearing loss disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• immunodeficiency disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF2	NM_001387220.1	c.406+2268C>A		intron_variant	Intron 5 of 8	ENST00000434687.6	NP_001374149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF2	ENST00000434687.6	c.406+2268C>A		intron_variant	Intron 5 of 8	5	NM_001387220.1	ENSP00000412869.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80351 AN: 151894 Hom.: 21916 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.562

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.529 AC: 80391 AN: 152012 Hom.: 21927 Cov.: 33 AF XY: 0.529 AC XY: 39304 AN XY: 74296

African (AFR) AF: 0.397 AC: 16467 AN: 41470

American (AMR) AF: 0.620 AC: 9453 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1818 AN: 3468

East Asian (EAS) AF: 0.757 AC: 3909 AN: 5166

South Asian (SAS) AF: 0.602 AC: 2906 AN: 4824

European-Finnish (FIN) AF: 0.506 AC: 5349 AN: 10578

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38459 AN: 67942

Other (OTH) AF: 0.559 AC: 1180 AN: 2110

Alfa AF: 0.526 Hom.: 5454

Bravo AF: 0.538

Asia WGS AF: 0.578 AC: 2008 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.41
PhyloP100		0.068
Mutation Taster		=100/0	polymorphism (auto)

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: rs9288462; hg19: chr2-213919289;