X-71108322-CA-TT

Variant names:

• chrX-71108322-CA-TT
• NM_000206.3:c.878_879delTGinsAA
• IL2RG p.Leu293Gln

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001438870.1(IL2RG):​c.781_782delTGinsAA​(p.Ter261Lysext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene IL2RG is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: not found (cov: 23)
• Consequence: IL2RG NM_001438870.1 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 0 publications found

Genes affected

IL2RG (HGNC:6010): (interleukin 2 receptor subunit gamma) The protein encoded by this gene is an important signaling component of many interleukin receptors, including those of interleukin -2, -4, -7 and -21, and is thus referred to as the common gamma chain. Mutations in this gene cause X-linked severe combined immunodeficiency (XSCID), as well as X-linked combined immunodeficiency (XCID), a less severe immunodeficiency disorder. [provided by RefSeq, Mar 2010]

IL2RG Gene-Disease associations (from GenCC):

• T-B+ severe combined immunodeficiency due to gamma chain deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women's Health, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285171 (HGNC:):

ACMG classification

Specifications for IL2RG are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Stoplost variant in NM_001438870.1 Downstream stopcodon found after 272 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438870.1. 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
	IL2RG	NM_000206.3	MANE Select	c.878_879delTGinsAA	p.Leu293Gln	missense	N/A	NP_000197.1	P31785-1
	IL2RG	NM_001438870.1		c.781_782delTGinsAA	p.Ter261Lysext*?	stop_lost	N/A	NP_001425799.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RG	ENST00000374202.7	TSL:1 MANE Select	c.878_879delTGinsAA	p.Leu293Gln	missense	N/A	ENSP00000363318.3	P31785-1
	ENSG00000285171	ENST00000646505.1		n.878_879delTGinsAA		non_coding_transcript_exon	Exon 7 of 12	ENSP00000496673.1	A0A2R8YE73
	IL2RG	ENST00000482750.6	TSL:5	c.781_782delTGinsAA	p.Ter261Lysext*?	stop_lost	N/A	ENSP00000421262.2	H0Y8J6

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-70328172;