rs1695526354

Variant names:

• chr2-213007987-G-T
• rs1695526354
• NM_001387220.1:c.954C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-213007987-G-T
• chr2-213007987-G-A

Variant summary

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

The NM_001387220.1(IKZF2):​c.954C>A​(p.Asp318Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000178 in 1,461,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: IKZF2 NM_001387220.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82
• 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.

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.954C>A	p.Asp318Glu	missense	Exon 9 of 9	NP_001374149.1	Q9UKS7-1
	IKZF2	NM_001371274.1		c.954C>A	p.Asp318Glu	missense	Exon 8 of 8	NP_001358203.1	Q9UKS7-1
	IKZF2	NM_016260.3		c.954C>A	p.Asp318Glu	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.954C>A	p.Asp318Glu	missense	Exon 9 of 9	ENSP00000412869.1	Q9UKS7-1
	IKZF2	ENST00000342002.6	TSL:1	c.972C>A	p.Asp324Glu	missense	Exon 8 of 8	ENSP00000342876.2	B4DWF2
	IKZF2	ENST00000374319.8	TSL:1	c.876C>A	p.Asp292Glu	missense	Exon 9 of 9	ENSP00000363439.4	Q9UKS7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461404 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 726984

African (AFR) AF: 0.00 AC: 0 AN: 33434

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111764

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.0075	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.8
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.26
Sift	Benign	0.20	T
Sift4G	Benign	0.086	T
Polyphen		0.99	D
Vest4		0.55
MutPred		0.55		Loss of catalytic residue at D318 (P = 0.0168)
MVP		0.46
MPC		0.86
ClinPred		0.96	D
GERP RS		6.0
Varity_R		0.44
gMVP		0.60
Mutation Taster		=47/53	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: rs1695526354; hg19: chr2-213872711;