ENST00000646505.1:n.925-34T>C

Variant names:

• chrX-71108342-T-G
• NM_000206.3:c.859A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000646505.1(ENSG00000285171):​n.859A>C variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ENSG00000285171 ENST00000646505.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3525293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RG	NM_000206.3	c.859A>C	p.Met287Leu	missense_variant	Exon 7 of 8	ENST00000374202.7	NP_000197.1
IL2RG	NM_001438870.1	c.762A>C	p.Arg254Arg	synonymous_variant	Exon 6 of 7		NP_001425799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RG	ENST00000374202.7	c.859A>C	p.Met287Leu	missense_variant	Exon 7 of 8	1	NM_000206.3	ENSP00000363318.3
ENSG00000285171	ENST00000646505.1	n.859A>C		non_coding_transcript_exon_variant	Exon 7 of 12			ENSP00000496673.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	17
DANN	Benign	0.80
DEOGEN2	Benign	0.42	T;.;.
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Uncertain	0.32	D
MutationAssessor	Benign	1.7	L;.;.
PhyloP100		2.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.75	N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.37	T;D;T
Sift4G	Benign	0.075	T;T;T
Polyphen		0.14	B;B;.
Vest4		0.26
MutPred		0.61		Loss of sheet (P = 0.0817);.;.;
MVP		0.93
MPC		0.55
ClinPred		0.32	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.54
Mutation Taster		=88/12	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

hg19: chrX-70328192;