rs2197025

Positions:

• chr2-213150581-A-G
• chr2-213150581-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKZF2	NM_001387220.1	c.-119-334T>C		intron_variant		ENST00000434687.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKZF2	ENST00000434687.6	c.-119-334T>C		intron_variant		5	NM_001387220.1	P4

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

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.341

Alfa AF: 0.415 Hom.: 13506

Bravo AF: 0.349

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.61

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: rs2197025; hg19: chr2-214015305;