chr2-213007950-C-T

Variant names:

• chr2-213007950-C-T
• NM_001387220.1:c.991G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001387220.1(IKZF2):​c.991G>A​(p.Glu331Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: IKZF2 NM_001387220.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99
• Publications: 0 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: AR, SD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3103298).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387220.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF2	NM_001387220.1	MANE Select	c.991G>A	p.Glu331Lys	missense	Exon 9 of 9	NP_001374149.1	Q9UKS7-1
	IKZF2	NM_001371274.1		c.991G>A	p.Glu331Lys	missense	Exon 8 of 8	NP_001358203.1	Q9UKS7-1
	IKZF2	NM_016260.3		c.991G>A	p.Glu331Lys	missense	Exon 8 of 8	NP_057344.2	Q9UKS7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF2	ENST00000434687.6	TSL:5 MANE Select	c.991G>A	p.Glu331Lys	missense	Exon 9 of 9	ENSP00000412869.1	Q9UKS7-1
	IKZF2	ENST00000342002.6	TSL:1	c.1009G>A	p.Glu337Lys	missense	Exon 8 of 8	ENSP00000342876.2	B4DWF2
	IKZF2	ENST00000374319.8	TSL:1	c.913G>A	p.Glu305Lys	missense	Exon 9 of 9	ENSP00000363439.4	Q9UKS7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461444 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727022

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111776

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.70	P
Vest4		0.48
MutPred		0.54		Gain of ubiquitination at E331 (P = 0.0162)
MVP		0.42
MPC		0.40
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.55
gMVP		0.60
Mutation Taster		=74/26	polymorphism

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

hg19: chr2-213872674;