NM_000206.3:c.1107C>A

Variant names:

• chrX-71107739-G-T
• rs1307151608
• NM_000206.3:c.1107C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000206.3(IL2RG):​c.1107C>A​(p.Thr369Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 112,259 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T369T) has been classified as Likely benign. The gene IL2RG is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL2RG NM_000206.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990
• 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

Specifications for IL2RG are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=0.99 with no splicing effect.

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.1107C>A	p.Thr369Thr	synonymous	Exon 8 of 8	NP_000197.1	P31785-1
	IL2RG	NM_001438870.1		c.*227C>A		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.1107C>A	p.Thr369Thr	synonymous	Exon 8 of 8	ENSP00000363318.3	P31785-1
	ENSG00000285171	ENST00000646505.1		n.924+538C>A		intron	N/A	ENSP00000496673.1	A0A2R8YE73
	IL2RG	ENST00000482750.6	TSL:5	c.*227C>A		3_prime_UTR	Exon 7 of 7	ENSP00000421262.2	H0Y8J6

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112259 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000648

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000807 AC: 1 AN: 123958 AF XY: 0.00

Gnomad AFR exome AF: 0.0000861

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: AC0 AF: 0.00 AC: 0 AN: 1020570 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 323508

African (AFR) AF: 0.00 AC: 0 AN: 23626

American (AMR) AF: 0.00 AC: 0 AN: 22105

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14779

East Asian (EAS) AF: 0.00 AC: 0 AN: 29204

South Asian (SAS) AF: 0.00 AC: 0 AN: 42356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 804455

Other (OTH) AF: 0.00 AC: 0 AN: 42611

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112259 Hom.: 0 Cov.: 23 AF XY: 0.0000291 AC XY: 1 AN XY: 34413

African (AFR) AF: 0.0000648 AC: 2 AN: 30850

American (AMR) AF: 0.00 AC: 0 AN: 10723

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3551

South Asian (SAS) AF: 0.00 AC: 0 AN: 2714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6179

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53159

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
DANN	Benign	0.60
PhyloP100		0.99

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: rs1307151608; hg19: chrX-70327589;