2-213019793-C-T

Variant names:

• chr2-213019793-C-T
• rs7569918
• NM_001387220.1:c.712+2200G>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.712+2200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,004 control chromosomes in the GnomAD database, including 6,121 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 0.27 (6121 hom., cov: 32)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 5 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

ENSG00000273118 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF2	NM_001387220.1	c.712+2200G>A		intron_variant	Intron 7 of 8	ENST00000434687.6	NP_001374149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF2	ENST00000434687.6	c.712+2200G>A		intron_variant	Intron 7 of 8	5	NM_001387220.1	ENSP00000412869.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41300 AN: 151886 Hom.: 6118 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.00962

Gnomad SAS AF: 0.0681

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.272 AC: 41324 AN: 152004 Hom.: 6121 Cov.: 32 AF XY: 0.266 AC XY: 19768 AN XY: 74322

African (AFR) AF: 0.347 AC: 14361 AN: 41428

American (AMR) AF: 0.193 AC: 2950 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1102 AN: 3470

East Asian (EAS) AF: 0.00964 AC: 50 AN: 5188

South Asian (SAS) AF: 0.0684 AC: 330 AN: 4826

European-Finnish (FIN) AF: 0.299 AC: 3152 AN: 10558

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.274 AC: 18589 AN: 67966

Other (OTH) AF: 0.256 AC: 541 AN: 2110

Alfa AF: 0.185 Hom.: 408

Bravo AF: 0.268

Asia WGS AF: 0.0690 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.34
PhyloP100		-0.11
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: rs7569918; hg19: chr2-213884517; COSMIC: COSV59584813; COSMIC: COSV59584813;