10-5966226-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002189.4(IL15RA):c.202G>A(p.Gly68Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000576 in 1,614,128 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )
Consequence
IL15RA
NM_002189.4 missense
NM_002189.4 missense
Scores
4
10
5
Clinical Significance
Conservation
PhyloP100: 3.68
Genes affected
IL15RA (HGNC:5978): (interleukin 15 receptor subunit alpha) This gene encodes a cytokine receptor that specifically binds interleukin 15 (IL15) with high affinity. The receptors of IL15 and IL2 share two subunits, IL2R beta and IL2R gamma. This forms the basis of many overlapping biological activities of IL15 and IL2. The protein encoded by this gene is structurally related to IL2R alpha, an additional IL2-specific alpha subunit necessary for high affinity IL2 binding. Unlike IL2RA, IL15RA is capable of binding IL15 with high affinity independent of other subunits, which suggests distinct roles between IL15 and IL2. This receptor is reported to enhance cell proliferation and expression of apoptosis inhibitor BCL2L1/BCL2-XL and BCL2. Multiple alternatively spliced transcript variants of this gene have been reported.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL15RA | NM_002189.4 | c.202G>A | p.Gly68Ser | missense_variant | 2/7 | ENST00000379977.8 | |
LOC107984200 | XR_001747348.2 | n.1458+1905C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL15RA | ENST00000379977.8 | c.202G>A | p.Gly68Ser | missense_variant | 2/7 | 1 | NM_002189.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251386Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135870
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GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461826Hom.: 0 Cov.: 31 AF XY: 0.0000564 AC XY: 41AN XY: 727216
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74470
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2024 | The c.202G>A (p.G68S) alteration is located in exon 2 (coding exon 2) of the IL15RA gene. This alteration results from a G to A substitution at nucleotide position 202, causing the glycine (G) at amino acid position 68 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;D;.;.;.;T;.;.;T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M;.;.;M;.;M;M;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;.;.;D;D;D;D;.;.;D;D
REVEL
Uncertain
Sift
Pathogenic
.;.;D;.;.;D;D;D;D;.;.;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;.;D
Polyphen
1.0
.;.;D;.;.;D;.;.;.;.;.;.;.
Vest4
MutPred
0.40
.;.;Loss of catalytic residue at A67 (P = 0.0575);.;.;Loss of catalytic residue at A67 (P = 0.0575);.;Loss of catalytic residue at A67 (P = 0.0575);Loss of catalytic residue at A67 (P = 0.0575);.;.;Loss of catalytic residue at A67 (P = 0.0575);.;
MVP
MPC
0.53
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at