rs1384396

Variant names:

• chr2-213018879-G-A
• rs1384396
• NM_001387220.1:c.712+3114C>T

Variant summary

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

The NM_001387220.1(IKZF2):​c.712+3114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,022 control chromosomes in the GnomAD database, including 4,096 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 0.22 (4096 hom., cov: 32)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• 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

ENSG00000273118 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387220.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF2	NM_001387220.1	MANE Select	c.712+3114C>T		intron	N/A	NP_001374149.1
	IKZF2	NM_001371274.1		c.712+3114C>T		intron	N/A	NP_001358203.1
	IKZF2	NM_016260.3		c.712+3114C>T		intron	N/A	NP_057344.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF2	ENST00000434687.6	TSL:5 MANE Select	c.712+3114C>T		intron	N/A	ENSP00000412869.1
	IKZF2	ENST00000342002.6	TSL:1	c.730+3114C>T		intron	N/A	ENSP00000342876.2
	IKZF2	ENST00000374319.8	TSL:1	c.634+3114C>T		intron	N/A	ENSP00000363439.4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33623 AN: 151904 Hom.: 4093 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.00962

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.221 AC: 33629 AN: 152022 Hom.: 4096 Cov.: 32 AF XY: 0.216 AC XY: 16043 AN XY: 74286

African (AFR) AF: 0.193 AC: 7995 AN: 41470

American (AMR) AF: 0.168 AC: 2566 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3468

East Asian (EAS) AF: 0.00965 AC: 50 AN: 5184

South Asian (SAS) AF: 0.0619 AC: 298 AN: 4812

European-Finnish (FIN) AF: 0.292 AC: 3077 AN: 10552

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17919 AN: 67962

Other (OTH) AF: 0.220 AC: 464 AN: 2106

Alfa AF: 0.255 Hom.: 737

Bravo AF: 0.211

Asia WGS AF: 0.0540 AC: 191 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.097
DANN	Benign	0.77
PhyloP100		-1.3
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: rs1384396; hg19: chr2-213883603;