rs10497993

Variant names:

• chr2-213105640-C-T
• rs10497993
• NM_001387220.1:c.139+42068G>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.139+42068G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 151,820 control chromosomes in the GnomAD database, including 216 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 0.038 (216 hom., cov: 31)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF2	NM_001387220.1	c.139+42068G>A		intron_variant	Intron 4 of 8	ENST00000434687.6	NP_001374149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF2	ENST00000434687.6	c.139+42068G>A		intron_variant	Intron 4 of 8	5	NM_001387220.1	ENSP00000412869.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5695 AN: 151702 Hom.: 215 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00906

Gnomad OTH AF: 0.0298

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

GnomAD4 genome AF: 0.0376 AC: 5710 AN: 151820 Hom.: 216 Cov.: 31 AF XY: 0.0376 AC XY: 2793 AN XY: 74184

African (AFR) AF: 0.103 AC: 4253 AN: 41316

American (AMR) AF: 0.0136 AC: 207 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3468

East Asian (EAS) AF: 0.0247 AC: 128 AN: 5178

South Asian (SAS) AF: 0.0250 AC: 120 AN: 4806

European-Finnish (FIN) AF: 0.0202 AC: 213 AN: 10534

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00908 AC: 617 AN: 67958

Other (OTH) AF: 0.0299 AC: 63 AN: 2106

Alfa AF: 0.0231 Hom.: 31

Bravo AF: 0.0399

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.42
PhyloP100		-1.8
Mutation Taster		=99/1	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: rs10497993; hg19: chr2-213970364;