NM_000206.3:c.1082dupC

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 2 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, Myriad Women’s Health
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285171 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -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,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000206.3. 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.1082dupC	p.Cys362MetfsTer7	frameshift	Exon 8 of 8	NP_000197.1	P31785-1
	IL2RG	NM_001438870.1		c.*202dupC		3_prime_UTR	Exon 7 of 7	NP_001425799.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RG	ENST00000374202.7	TSL:1 MANE Select	c.1082dupC	p.Cys362MetfsTer7	frameshift	Exon 8 of 8	ENSP00000363318.3	P31785-1
	ENSG00000285171	ENST00000646505.1		n.924+513dupC		intron	N/A	ENSP00000496673.1	A0A2R8YE73
	IL2RG	ENST00000482750.6	TSL:5	c.*202dupC		3_prime_UTR	Exon 7 of 7	ENSP00000421262.2	H0Y8J6

Frequencies

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

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

GnomAD2 exomes AF: 0.0000228 AC: 3 AN: 131677 AF XY: 0.0000240

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000592

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000319

Gnomad OTH exome 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

African (AFR) AF: 0.00 AC: 0 AN: 24109

American (AMR) AF: 0.00 AC: 0 AN: 24390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15553

East Asian (EAS) AF: 0.00 AC: 0 AN: 29578

South Asian (SAS) AF: 0.00 AC: 0 AN: 45114

European-Finnish (FIN) AF: 0.0000522 AC: 2 AN: 38296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3835

European-Non Finnish (NFE) AF: 0.00000738 AC: 6 AN: 813025

Other (OTH) AF: 0.00 AC: 0 AN: 43350

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

African (AFR) AF: 0.0000651 AC: 2 AN: 30719

American (AMR) AF: 0.00 AC: 0 AN: 10687

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3530

South Asian (SAS) AF: 0.00 AC: 0 AN: 2700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52995

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0
Mutation Taster		=49/151	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: rs745545309; hg19: chrX-70327613; COSMIC: COSV52147804; COSMIC: COSV52147804;