X-71107798-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_000206.3(IL2RG):c.1048C>T(p.Pro350Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,181,598 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.0000094 ( 0 hom. 0 hem. )

Consequence

IL2RG
NM_000206.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.916

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14546299).

BP6

Variant X-71107798-G-A is Benign according to our data. Variant chrX-71107798-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2058786.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000622 (7/112455) while in subpopulation AMR AF= 0.000651 (7/10754). AF 95% confidence interval is 0.000305. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL2RG	NM_000206.3 linkuse as main transcript	c.1048C>T	p.Pro350Ser	missense_variant	8/8	ENST00000374202.7
IL2RG	XM_047442089.1 linkuse as main transcript	c.*168C>T		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RG	ENST00000374202.7 linkuse as main transcript	c.1048C>T	p.Pro350Ser	missense_variant	8/8	1	NM_000206.3	P1	P31785-1

Frequencies

GnomAD3 genomes

AF:

0.0000622

AC:

AN:

112455

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

34611

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000651

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

GnomAD3 exomes

AF:

0.0000521

AC:

AN:

153444

Hom.:

AF XY:

0.00

AC XY:

AN XY:

47262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000361

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

AF:

0.00000935

AC:

AN:

1069143

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

344785

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000328

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

AF:

0.0000622

AC:

AN:

112455

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

34611

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000651

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

X-linked severe combined immunodeficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Uncertain

-0.060

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Uncertain

0.56

D;.;.

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.82

T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Uncertain

0.59

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.89

N;N;N

REVEL

Uncertain

0.37

Sift

Benign

0.087

T;T;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.26

B;D;.

Vest4

0.086

MutPred

0.17

Gain of loop (P = 0.0435);.;.;

MVP

0.86

MPC

0.64

ClinPred

0.12

GERP RS

4.2

Varity_R

0.051

gMVP

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over