dbSNP rs7880291: IL2RG:c.115+187C>G (chrX-71111238-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000206.3(IL2RG):c.115+187C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000295 in 712,445 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.000030 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000029 ( 0 hom. 3 hem. )

Consequence

IL2RG
NM_000206.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

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

IL2RG links:

ENSG00000285171 (HGNC:):

ENSG00000285171 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BS2

High Hemizygotes in GnomAdExome4 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.115+187C>G		intron	N/A	NP_000197.1	P31785-1
	IL2RG	NM_001438870.1		c.115+187C>G		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.115+187C>G	intron	N/A	ENSP00000363318.3	P31785-1
ENSG00000285171	ENST00000646505.1		n.115+187C>G	intron	N/A	ENSP00000496673.1	A0A2R8YE73
IL2RG	ENST00000482750.6	TSL:5	c.115+187C>G	intron	N/A	ENSP00000421262.2	H0Y8J6

Frequencies

GnomAD3 genomes

AF:

0.0000304

AC:

AN:

98814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000351

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:

0.0000435

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000293

AC:

AN:

613631

Hom.:

Cov.:

AF XY:

0.0000185

AC XY:

AN XY:

162279

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15620

American (AMR)

AF:

0.0000976

AC:

AN:

20499

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13545

East Asian (EAS)

AF:

0.00

AC:

AN:

25061

South Asian (SAS)

AF:

0.000139

AC:

AN:

36005

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27969

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1931

European-Non Finnish (NFE)

AF:

0.0000248

AC:

AN:

443630

Other (OTH)

AF:

0.00

AC:

AN:

29371

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000304

AC:

AN:

98814

Hom.:

Cov.:

AF XY:

0.0000393

AC XY:

AN XY:

25448

show subpopulations

African (AFR)

AF:

0.0000351

AC:

AN:

28476

American (AMR)

AF:

0.00

AC:

AN:

9445

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2035

East Asian (EAS)

AF:

0.00

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4927

Middle Eastern (MID)

AF:

0.00

AC:

AN:

165

European-Non Finnish (NFE)

AF:

0.0000435

AC:

AN:

45939

Other (OTH)

AF:

0.00

AC:

AN:

1271

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 Het

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:

0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.16

(source)

DANN

Benign

0.41

PhyloP100

-2.0

PromoterAI

-0.0086

Neutral

(source)

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

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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