rs2197025

Variant names:

• chr2-213150581-A-G
• rs2197025
• NM_001387220.1:c.-119-334T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-213150581-A-G
• chr2-213150581-A-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.-119-334T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,006 control chromosomes in the GnomAD database, including 11,309 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 0.37 (11309 hom., cov: 26)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 5 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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 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.-119-334T>C		intron	N/A	NP_001374149.1
	IKZF2	NM_001371274.1		c.-16+1545T>C		intron	N/A	NP_001358203.1
	IKZF2	NM_001079526.2		c.-119-334T>C		intron	N/A	NP_001072994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF2	ENST00000434687.6	TSL:5 MANE Select	c.-119-334T>C		intron	N/A	ENSP00000412869.1
	IKZF2	ENST00000374319.8	TSL:1	c.-119-334T>C		intron	N/A	ENSP00000363439.4
	IKZF2	ENST00000457361.5	TSL:5	c.-248-334T>C		intron	N/A	ENSP00000410447.2

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55435 AN: 150890 Hom.: 11311 Cov.: 26

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.367 AC: 55429 AN: 151006 Hom.: 11309 Cov.: 26 AF XY: 0.371 AC XY: 27348 AN XY: 73658

African (AFR) AF: 0.197 AC: 8083 AN: 41130

American (AMR) AF: 0.352 AC: 5335 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1215 AN: 3442

East Asian (EAS) AF: 0.476 AC: 2433 AN: 5110

South Asian (SAS) AF: 0.321 AC: 1529 AN: 4766

European-Finnish (FIN) AF: 0.565 AC: 5878 AN: 10398

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29668 AN: 67704

Other (OTH) AF: 0.341 AC: 714 AN: 2092

Alfa AF: 0.405 Hom.: 16952

Bravo AF: 0.349

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.61
PhyloP100		2.6
PromoterAI		-0.053	Neutral
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: rs2197025; hg19: chr2-214015305;