rs137852509

chrX-71108278-G-AchrX-71108278-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000206.3(IL2RG):c.923C>T(p.Ser308Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,194,295 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S308S) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000013 (0 hom. 6 hem.)
• Consequence: IL2RG NM_000206.3 missense, splice_region
• Scores: Splicing: ADA: 0.06424
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RG	NM_000206.3	c.923C>T	p.Ser308Leu	missense_variant, splice_region_variant	7/8	ENST00000374202.7
IL2RG	XM_047442089.1	c.*43C>T		splice_region_variant, 3_prime_UTR_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RG	ENST00000374202.7	c.923C>T	p.Ser308Leu	missense_variant, splice_region_variant	7/8	1	NM_000206.3	P1

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111576 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 33760

Gnomad AFR AF: 0.00

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: 0.000166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000546 AC: 1 AN: 183284 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67734

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000625

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 14 AN: 1082719 Hom.: 0 Cov.: 28 AF XY: 0.0000171 AC XY: 6 AN XY: 350065

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: 0.0000186

Gnomad4 FIN exome AF: 0.0000740

Gnomad4 NFE exome AF: 0.0000109

Gnomad4 OTH exome AF: 0.0000219

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111576 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 33760

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000166

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;.;.
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Pathogenic	0.72	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.4	M;.;.
MutationTaster	Benign	0.59	D;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.3	N;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.020	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.96	D;B;.
Vest4		0.25
MutPred		0.48		Loss of sheet (P = 0.0037);.;.;
MVP		0.95
MPC		0.53
ClinPred		0.63	D
GERP RS		4.2
Varity_R		0.22
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.064
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.030		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: rs137852509; hg19: chrX-70328128; COSMIC: COSV52148892; COSMIC: COSV52148892;