chr2-213074658-C-T

Variant names:

• chr2-213074658-C-T
• rs1384398
• NM_001387220.1:c.140-17559G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

IKZF2 Gene-Disease associations (from GenCC):

• HELIOS deficiency

  Inheritance: SD, AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• hearing loss disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• immunodeficiency disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IKZF2	NM_001387220.1	c.140-17559G>A		intron_variant	Intron 4 of 8	ENST00000434687.6	NP_001374149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF2	ENST00000434687.6	c.140-17559G>A		intron_variant	Intron 4 of 8	5	NM_001387220.1	ENSP00000412869.1

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

African (AFR) AF: 0.113 AC: 4709 AN: 41522

American (AMR) AF: 0.0237 AC: 363 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0450 AC: 156 AN: 3470

East Asian (EAS) AF: 0.0249 AC: 129 AN: 5182

South Asian (SAS) AF: 0.0293 AC: 141 AN: 4820

European-Finnish (FIN) AF: 0.0240 AC: 254 AN: 10602

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0202 AC: 1370 AN: 67988

Other (OTH) AF: 0.0482 AC: 102 AN: 2114

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
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1384398; hg19: chr2-213939382;