rs372985214

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000206.3(IL2RG):c.855-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,132,849 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★). The gene IL2RG is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000019 ( 0 hom. 4 hem. )

Consequence

IL2RG
NM_000206.3 splice_region, intron

Scores

Splicing: ADA: 0.00003901

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.436

Publications

0 publications found

Variant links:

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: Myriad Women's Health, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet
Omenn syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IL2RG links:

ENSG00000285171 (HGNC:):

ENSG00000285171 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000206.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

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

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-71108354-G-A is Benign according to our data. Variant chrX-71108354-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 463386.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000806 (9/111682) while in subpopulation AFR AF = 0.000293 (9/30665). AF 95% confidence interval is 0.000152. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 3 XL,AR gene

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.855-8C>T		splice_region intron	N/A	NP_000197.1	P31785-1
	IL2RG	NM_001438870.1		c.758-8C>T		splice_region intron	N/A	NP_001425799.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL2RG	ENST00000374202.7	TSL:1 MANE Select	c.855-8C>T	splice_region intron	N/A	ENSP00000363318.3	P31785-1
ENSG00000285171	ENST00000646505.1		n.855-8C>T	splice_region intron	N/A	ENSP00000496673.1	A0A2R8YE73
IL2RG	ENST00000482750.6	TSL:5	c.758-8C>T	splice_region intron	N/A	ENSP00000421262.2	H0Y8J6

Frequencies

GnomAD3 genomes

AF:

0.0000806

AC:

AN:

111682

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000293

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:

0.0000600

AC:

AN:

183273

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000837

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

AF:

0.0000186

AC:

AN:

1021167

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

298855

show subpopulations

African (AFR)

AF:

0.000720

AC:

AN:

24997

American (AMR)

AF:

0.00

AC:

AN:

35131

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18915

East Asian (EAS)

AF:

0.00

AC:

AN:

29900

South Asian (SAS)

AF:

0.00

AC:

AN:

52335

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3902

European-Non Finnish (NFE)

AF:

0.00000130

AC:

AN:

771846

Other (OTH)

AF:

0.00

AC:

AN:

43621

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000806

AC:

AN:

111682

Hom.:

Cov.:

AF XY:

0.0000887

AC XY:

AN XY:

33838

show subpopulations

African (AFR)

AF:

0.000293

AC:

AN:

30665

American (AMR)

AF:

0.00

AC:

AN:

10503

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3579

South Asian (SAS)

AF:

0.00

AC:

AN:

2670

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53140

Other (OTH)

AF:

0.00

AC:

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000136

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

X-linked severe combined immunodeficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.48

(source)

DANN

Benign

0.75

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000039

dbscSNV1_RF

Benign

0.028

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over