2-213008144-A-C

Variant names:

• chr2-213008144-A-C
• rs76705042
• NM_001387220.1:c.857-60T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001387220.1(IKZF2):​c.857-60T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,473,000 control chromosomes in the GnomAD database, including 43,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4043 hom., cov: 31)
  • Exomes 𝑓: 0.24 (39927 hom.)
• Consequence: IKZF2 NM_001387220.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.765
• 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

ENSG00000273118 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-213008144-A-C is Benign according to our data. Variant chr2-213008144-A-C is described in ClinVar as [Benign]. Clinvar id is 2688165.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF2	NM_001387220.1	c.857-60T>G		intron_variant	Intron 8 of 8	ENST00000434687.6	NP_001374149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF2	ENST00000434687.6	c.857-60T>G		intron_variant	Intron 8 of 8	5	NM_001387220.1	ENSP00000412869.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33288 AN: 151200 Hom.: 4039 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.236 AC: 311948 AN: 1321696 Hom.: 39927 AF XY: 0.232 AC XY: 150102 AN XY: 646742

African (AFR) AF: 0.194 AC: 5534 AN: 28496

American (AMR) AF: 0.133 AC: 3313 AN: 24838

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 5314 AN: 19540

East Asian (EAS) AF: 0.00142 AC: 52 AN: 36674

South Asian (SAS) AF: 0.0765 AC: 4981 AN: 65074

European-Finnish (FIN) AF: 0.291 AC: 13760 AN: 47334

Middle Eastern (MID) AF: 0.154 AC: 697 AN: 4512

European-Non Finnish (NFE) AF: 0.256 AC: 266422 AN: 1040648

Other (OTH) AF: 0.218 AC: 11875 AN: 54580

GnomAD4 genome AF: 0.220 AC: 33294 AN: 151304 Hom.: 4043 Cov.: 31 AF XY: 0.214 AC XY: 15815 AN XY: 73842

African (AFR) AF: 0.193 AC: 7953 AN: 41274

American (AMR) AF: 0.167 AC: 2539 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3464

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5158

South Asian (SAS) AF: 0.0660 AC: 317 AN: 4806

European-Finnish (FIN) AF: 0.283 AC: 2921 AN: 10310

Middle Eastern (MID) AF: 0.233 AC: 67 AN: 288

European-Non Finnish (NFE) AF: 0.263 AC: 17848 AN: 67762

Other (OTH) AF: 0.218 AC: 458 AN: 2102

Alfa AF: 0.243 Hom.: 615

Bravo AF: 0.212

Asia WGS AF: 0.0550 AC: 193 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		-0.77
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: rs76705042; hg19: chr2-213872868;