NM_001387220.1:c.406+2268C>A

Variant names:

• chr2-213054565-G-T
• rs9288462
• NM_001387220.1:c.406+2268C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387220.1(IKZF2):​c.406+2268C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,012 control chromosomes in the GnomAD database, including 21,927 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 0.53 (21927 hom., cov: 33)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF2	NM_001387220.1	c.406+2268C>A		intron_variant	Intron 5 of 8	ENST00000434687.6	NP_001374149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF2	ENST00000434687.6	c.406+2268C>A		intron_variant	Intron 5 of 8	5	NM_001387220.1	ENSP00000412869.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80351 AN: 151894 Hom.: 21916 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.529 AC: 80391 AN: 152012 Hom.: 21927 Cov.: 33 AF XY: 0.529 AC XY: 39304 AN XY: 74296

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.559

Alfa AF: 0.394 Hom.: 1101

Bravo AF: 0.538

Asia WGS AF: 0.578 AC: 2008 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.41

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: rs9288462; hg19: chr2-213919289;