rs768291371

Variant names:

• chrX-71107755-G-A
• rs768291371
• NM_000206.3:c.1091C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-71107755-G-A
• chrX-71107755-G-T

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.1091C>T​(p.Thr364Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,032,392 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T364N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000019 (0 hom. 0 hem.)
• Consequence: IL2RG NM_000206.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, 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=0.1250968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RG	NM_000206.3	c.1091C>T	p.Thr364Ile	missense_variant	Exon 8 of 8	ENST00000374202.7	NP_000197.1
IL2RG	NM_001438870.1	c.*211C>T		3_prime_UTR_variant	Exon 7 of 7		NP_001425799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RG	ENST00000374202.7	c.1091C>T	p.Thr364Ile	missense_variant	Exon 8 of 8	1	NM_000206.3	ENSP00000363318.3
ENSG00000285171	ENST00000646505.1	n.924+522C>T		intron_variant	Intron 7 of 11			ENSP00000496673.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000230 AC: 3 AN: 130526 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000603

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000173

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000194 AC: 2 AN: 1032392 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 329656

African (AFR) AF: 0.00 AC: 0 AN: 23996

American (AMR) AF: 0.0000420 AC: 1 AN: 23822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15296

East Asian (EAS) AF: 0.0000339 AC: 1 AN: 29476

South Asian (SAS) AF: 0.00 AC: 0 AN: 44331

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38109

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3799

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 810447

Other (OTH) AF: 0.00 AC: 0 AN: 43116

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Uncertain	0.42	T;.;.
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.1	M;.;.
PhyloP100		0.36
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.11	N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.045	D;D;D
Polyphen		0.0010	B;B;.
Vest4		0.14
MutPred		0.24		Loss of glycosylation at T364 (P = 0.0162);.;.;
MVP		0.60
MPC		0.91
ClinPred		0.057	T
GERP RS		1.3
Varity_R		0.079
gMVP		0.24
Mutation Taster		=89/11	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: rs768291371; hg19: chrX-70327605;