rs10497994

Variant names:

• chr2-213107780-T-C
• rs10497994
• NM_001387220.1:c.139+39928A>G

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+39928A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 152,252 control chromosomes in the GnomAD database, including 254 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 0.040 (254 hom., cov: 32)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF2	NM_001387220.1	c.139+39928A>G		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+39928A>G		intron_variant	Intron 4 of 8	5	NM_001387220.1	ENSP00000412869.1

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6052 AN: 152134 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00923

Gnomad OTH AF: 0.0355

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

GnomAD4 genome AF: 0.0399 AC: 6074 AN: 152252 Hom.: 254 Cov.: 32 AF XY: 0.0396 AC XY: 2945 AN XY: 74456

African (AFR) AF: 0.110 AC: 4582 AN: 41538

American (AMR) AF: 0.0130 AC: 199 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3470

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5188

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4822

European-Finnish (FIN) AF: 0.0211 AC: 224 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00925 AC: 629 AN: 68016

Other (OTH) AF: 0.0356 AC: 75 AN: 2108

Alfa AF: 0.0295 Hom.: 22

Bravo AF: 0.0415

Asia WGS AF: 0.0360 AC: 126 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.093
DANN	Benign	0.48
PhyloP100		-2.0
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: rs10497994; hg19: chr2-213972504;