rs1695482697

Variant names:

• chr2-213007690-G-C
• rs1695482697
• NM_001387220.1:c.1251C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001387220.1(IKZF2):​c.1251C>G​(p.His417Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IKZF2 NM_001387220.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11168048).

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.1251C>G	p.His417Gln	missense	Exon 9 of 9	NP_001374149.1	Q9UKS7-1
	IKZF2	NM_001371274.1		c.1251C>G	p.His417Gln	missense	Exon 8 of 8	NP_001358203.1	Q9UKS7-1
	IKZF2	NM_016260.3		c.1251C>G	p.His417Gln	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.1251C>G	p.His417Gln	missense	Exon 9 of 9	ENSP00000412869.1	Q9UKS7-1
	IKZF2	ENST00000342002.6	TSL:1	c.1269C>G	p.His423Gln	missense	Exon 8 of 8	ENSP00000342876.2	B4DWF2
	IKZF2	ENST00000374319.8	TSL:1	c.1173C>G	p.His391Gln	missense	Exon 9 of 9	ENSP00000363439.4	Q9UKS7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461576 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727092

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111790

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.063
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.12
Sift	Benign	0.25	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.30
MutPred		0.25		Loss of catalytic residue at D416 (P = 0.1221)
MVP		0.082
MPC		0.25
ClinPred		0.37	T
GERP RS		6.1
Varity_R		0.14
gMVP		0.29
Mutation Taster		=84/16	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

dbSNP: rs1695482697; hg19: chr2-213872414;