chrX-71107763-T-TG

Variant names:

• chrX-71107763-T-TG
• rs745545309
• NM_000206.3:c.1082dupC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_Moderate BS2

The NM_000206.3(IL2RG):​c.1082dupC​(p.Cys362MetfsTer7) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000087 in 1,149,082 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000077 (0 hom. 2 hem.)
• Consequence: IL2RG NM_000206.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00

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]

ENSG00000285171 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0252 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RG	NM_000206.3	c.1082dupC	p.Cys362MetfsTer7	frameshift_variant	Exon 8 of 8	ENST00000374202.7	NP_000197.1
IL2RG	XM_047442089.1	c.*202dupC		3_prime_UTR_variant	Exon 7 of 7		XP_047298045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RG	ENST00000374202.7	c.1082dupC	p.Cys362MetfsTer7	frameshift_variant	Exon 8 of 8	1	NM_000206.3	ENSP00000363318.3
ENSG00000285171	ENST00000646505.1	n.924+513dupC		intron_variant	Intron 7 of 11			ENSP00000496673.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111832 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34066

Gnomad AFR AF: 0.0000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000771 AC: 8 AN: 1037250 Hom.: 0 Cov.: 29 AF XY: 0.00000602 AC XY: 2 AN XY: 332108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000522

Gnomad4 NFE exome AF: 0.00000738

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111832 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34066

Gnomad4 AFR AF: 0.0000651

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs745545309; hg19: chrX-70327613;