chr2-213007418-C-G

Variant names:

• chr2-213007418-C-G
• rs1270564182
• NM_001387220.1:c.1523G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001387220.1(IKZF2):​c.1523G>C​(p.Ser508Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IKZF2 NM_001387220.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1523G>C	p.Ser508Thr	missense	Exon 9 of 9	NP_001374149.1	Q9UKS7-1
	IKZF2	NM_001371274.1		c.1523G>C	p.Ser508Thr	missense	Exon 8 of 8	NP_001358203.1	Q9UKS7-1
	IKZF2	NM_016260.3		c.1523G>C	p.Ser508Thr	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.1523G>C	p.Ser508Thr	missense	Exon 9 of 9	ENSP00000412869.1	Q9UKS7-1
	IKZF2	ENST00000342002.6	TSL:1	c.1541G>C	p.Ser514Thr	missense	Exon 8 of 8	ENSP00000342876.2	B4DWF2
	IKZF2	ENST00000374319.8	TSL:1	c.1445G>C	p.Ser482Thr	missense	Exon 9 of 9	ENSP00000363439.4	Q9UKS7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.27
Sift	Benign	0.033	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.83	P
Vest4		0.62
MutPred		0.81		Loss of disorder (P = 0.0622)
MVP		0.19
MPC		0.38
ClinPred		0.78	D
GERP RS		5.7
Varity_R		0.54
gMVP		0.48
Mutation Taster		=44/56	disease causing

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: rs1270564182; hg19: chr2-213872142;