2-213013916-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001387220.1(IKZF2):c.731G>C(p.Cys244Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C244F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IKZF2
NM_001387220.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.93

Publications

1 publications found

Variant links:

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

IKZF2 links:

ENSG00000273118 (HGNC:):

ENSG00000273118 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.24738792).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IKZF2	NM_001387220.1	MANE Select	c.731G>C	p.Cys244Ser	missense	Exon 8 of 9	NP_001374149.1	Q9UKS7-1
IKZF2	NM_001371274.1		c.731G>C	p.Cys244Ser	missense	Exon 7 of 8	NP_001358203.1	Q9UKS7-1
IKZF2	NM_016260.3		c.731G>C	p.Cys244Ser	missense	Exon 7 of 8	NP_057344.2	Q9UKS7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IKZF2	ENST00000434687.6	TSL:5 MANE Select	c.731G>C	p.Cys244Ser	missense	Exon 8 of 9	ENSP00000412869.1	Q9UKS7-1
IKZF2	ENST00000342002.6	TSL:1	c.749G>C	p.Cys250Ser	missense	Exon 7 of 8	ENSP00000342876.2	B4DWF2
IKZF2	ENST00000374319.8	TSL:1	c.653G>C	p.Cys218Ser	missense	Exon 8 of 9	ENSP00000363439.4	Q9UKS7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250708

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459334

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725988

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33374

American (AMR)

AF:

0.00

AC:

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26032

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110134

Other (OTH)

AF:

0.00

AC:

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.16

Eigen

Benign

-0.015

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0070

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

5.9

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.86

Sift4G

Benign

0.27

Polyphen

0.17

Vest4

0.81

MutPred

0.58

Loss of loop (P = 0.0112)

MVP

0.12

MPC

0.33

ClinPred

0.30

GERP RS

5.4

Varity_R

0.32

gMVP

0.47

Mutation Taster

=75/25

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over