rs10932460

Variant names:

• chr2-213035748-T-A
• rs10932460
• NM_001387220.1:c.575-13618A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-213035748-T-A
• chr2-213035748-T-C

Variant summary

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

The NM_001387220.1(IKZF2):​c.575-13618A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,982 control chromosomes in the GnomAD database, including 13,798 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 0.38 (13798 hom., cov: 32)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF2	NM_001387220.1	c.575-13618A>T		intron_variant	Intron 6 of 8	ENST00000434687.6	NP_001374149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF2	ENST00000434687.6	c.575-13618A>T		intron_variant	Intron 6 of 8	5	NM_001387220.1	ENSP00000412869.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58486 AN: 151864 Hom.: 13795 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.385 AC: 58493 AN: 151982 Hom.: 13798 Cov.: 32 AF XY: 0.389 AC XY: 28915 AN XY: 74272

African (AFR) AF: 0.107 AC: 4452 AN: 41500

American (AMR) AF: 0.538 AC: 8216 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3987 AN: 5174

South Asian (SAS) AF: 0.369 AC: 1773 AN: 4806

European-Finnish (FIN) AF: 0.466 AC: 4910 AN: 10532

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32082 AN: 67922

Other (OTH) AF: 0.418 AC: 883 AN: 2112

Alfa AF: 0.408 Hom.: 1752

Bravo AF: 0.387

Asia WGS AF: 0.486 AC: 1688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.9
DANN	Benign	0.85
PhyloP100		0.066
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: rs10932460; hg19: chr2-213900472;