rs2228059

Positions:

• chr10-5960405-T-C
• chr10-5960405-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002189.4(IL15RA):​c.545A>G​(p.Asn182Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N182T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: IL15RA NM_002189.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06165555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15RA	NM_002189.4	c.545A>G	p.Asn182Ser	missense_variant	4/7	ENST00000379977.8	NP_002180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8	c.545A>G	p.Asn182Ser	missense_variant	4/7	1	NM_002189.4	ENSP00000369312	A2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.9
DANN	Benign	0.74
DEOGEN2	Benign	0.0082	.;T;T;.;.;.;.;.;T;.;.;T;.;T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.59	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.062	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;.;N;.;.;.;.;.;.;.;N;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.47	.;.;N;.;.;N;N;N;.;N;N;.;.;N;N
REVEL	Benign	0.037
Sift	Benign	0.083	.;.;T;.;.;D;T;T;.;T;T;.;.;D;T
Sift4G	Benign	0.63	T;T;T;T;T;T;T;T;T;T;T;T;T;.;T
Polyphen		0.0020	.;.;B;.;.;B;.;.;.;.;.;.;.;.;.
Vest4		0.048
MutPred		0.069		.;.;Gain of phosphorylation at N182 (P = 0.0612);.;.;.;.;.;.;.;Gain of phosphorylation at N182 (P = 0.0612);.;.;.;.;
MVP		0.34
MPC		0.084
ClinPred		0.020	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.060

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs2228059; hg19: chr10-6002368;