2-213008144-A-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000273118 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.00142

Gnomad4 SAS exome AF: 0.0765

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.218

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

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0660

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.218

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

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: rs76705042; hg19: chr2-213872868;