NM_000206.3:c.1094T>C

Variant names:

• chrX-71107752-A-G
• rs1602287912
• NM_000206.3:c.1094T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000206.3(IL2RG):​c.1094T>C​(p.Leu365Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL2RG NM_000206.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.883
• 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: 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22056901).

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.1094T>C	p.Leu365Pro	missense	Exon 8 of 8	NP_000197.1	P31785-1
	IL2RG	NM_001438870.1		c.*214T>C		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.1094T>C	p.Leu365Pro	missense	Exon 8 of 8	ENSP00000363318.3	P31785-1
	ENSG00000285171	ENST00000646505.1		n.924+525T>C		intron	N/A	ENSP00000496673.1	A0A2R8YE73
	IL2RG	ENST00000482750.6	TSL:5	c.*214T>C		3_prime_UTR	Exon 7 of 7	ENSP00000421262.2	H0Y8J6

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1029395 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 328077

African (AFR) AF: 0.00 AC: 0 AN: 23886

American (AMR) AF: 0.00 AC: 0 AN: 23400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15149

East Asian (EAS) AF: 0.00 AC: 0 AN: 29390

South Asian (SAS) AF: 0.00 AC: 0 AN: 43821

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38025

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3788

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 808947

Other (OTH) AF: 0.00 AC: 0 AN: 42989

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	X-linked severe combined immunodeficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	12
DANN	Benign	0.53
DEOGEN2	Uncertain	0.50	T
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.88
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.43	N
REVEL	Uncertain	0.37
Sift	Benign	0.057	T
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.30
MutPred		0.32		Loss of stability (P = 0.0088)
MVP		0.85
MPC		1.1
ClinPred		0.28	T
GERP RS		3.2
Varity_R		0.12
gMVP		0.52
Mutation Taster		=81/19	polymorphism

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: rs1602287912; hg19: chrX-70327602;