rs10497993

Positions:

• chr2-213105640-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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/exons	MANE	Protein	UniProt
IKZF2	NM_001387220.1	c.139+42068G>A		intron_variant		ENST00000434687.6	NP_001374149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKZF2	ENST00000434687.6	c.139+42068G>A		intron_variant		5	NM_001387220.1	ENSP00000412869	P4

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

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.0250

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.00908

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0280 Hom.: 17

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

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: rs10497993; hg19: chr2-213970364;