rs10932460

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IKZF2	NM_001387220.1	c.575-13618A>T		intron_variant		ENST00000434687.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKZF2	ENST00000434687.6	c.575-13618A>T		intron_variant		5	NM_001387220.1	P4

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

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.418

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10932460; hg19: chr2-213900472;