rs1384398

Positions:

• chr2-213074658-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.140-17559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 152,188 control chromosomes in the GnomAD database, including 297 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 0.048 (297 hom., cov: 33)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKZF2	NM_001387220.1	c.140-17559G>A		intron_variant		ENST00000434687.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKZF2	ENST00000434687.6	c.140-17559G>A		intron_variant		5	NM_001387220.1	P4

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 7228 AN: 152070 Hom.: 295 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0483

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

GnomAD4 genome AF: 0.0476 AC: 7248 AN: 152188 Hom.: 297 Cov.: 33 AF XY: 0.0468 AC XY: 3482 AN XY: 74398

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0237

Gnomad4 ASJ AF: 0.0450

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.0293

Gnomad4 FIN AF: 0.0240

Gnomad4 NFE AF: 0.0202

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0327 Hom.: 39

Bravo AF: 0.0499

Asia WGS AF: 0.0360 AC: 128 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.57

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: rs1384398; hg19: chr2-213939382;