X-71107780-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_000206.3(IL2RG):c.1066C>T(p.Pro356Ser) 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL2RG NM_000206.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25717467).
• BP6: Variant X-71107780-G-A is Benign according to our data. Variant chrX-71107780-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 833874.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RG	NM_000206.3	c.1066C>T	p.Pro356Ser	missense_variant	8/8	ENST00000374202.7
IL2RG	XM_047442089.1	c.*186C>T		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RG	ENST00000374202.7	c.1066C>T	p.Pro356Ser	missense_variant	8/8	1	NM_000206.3	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000686 AC: 1 AN: 145705 Hom.: 0 AF XY: 0.0000221 AC XY: 1 AN XY: 45279

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000484

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.44e-7 AC: 1 AN: 1058970 Hom.: 0 Cov.: 29 AF XY: 0.00000293 AC XY: 1 AN XY: 341110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000349

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

X-linked severe combined immunodeficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Uncertain	-0.010
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;.;.
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	0.94	N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N;D;N
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;B;.
Vest4		0.12
MutPred		0.31		Gain of loop (P = 0.0851);.;.;
MVP		0.96
MPC		0.61
ClinPred		0.69	D
GERP RS		3.4
Varity_R		0.21
gMVP		0.63

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: rs760735556; hg19: chrX-70327630;