rs587776729

Positions:

• chrX-71109273-T-TCCAATGCTG

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PM4 PP5

The ENST00000374202.7(IL2RG):​c.711_712insCAGCATTGG​(p.Gln235_Trp237dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: IL2RG ENST00000374202.7 inframe_insertion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.30

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in ENST00000374202.7
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000374202.7.
• PP5: Variant X-71109273-T-TCCAATGCTG is Pathogenic according to our data. Variant chrX-71109273-T-TCCAATGCTG is described in ClinVar as [Pathogenic]. Clinvar id is 10024.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL2RG	NM_000206.3	c.711_712insCAGCATTGG	p.Gln235_Trp237dup	inframe_insertion	5/8	ENST00000374202.7	NP_000197.1
IL2RG	XM_047442089.1	c.711_712insCAGCATTGG	p.Gln235_Trp237dup	inframe_insertion	5/7		XP_047298045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RG	ENST00000374202.7	c.711_712insCAGCATTGG	p.Gln235_Trp237dup	inframe_insertion	5/8	1	NM_000206.3	ENSP00000363318	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

X-linked severe combined immunodeficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 1995

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587776729; hg19: chrX-70329123;