NM_002189.4:c.545A>T

Variant names:

• chr10-5960405-T-A
• rs2228059
• NM_002189.4:c.545A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002189.4(IL15RA):​c.545A>T​(p.Asn182Ile) 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. 15/22 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 Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: IL15RA NM_002189.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 0 publications found

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]

ENSG00000300557 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074506134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15RA	NM_002189.4	c.545A>T	p.Asn182Ile	missense_variant	Exon 4 of 7	ENST00000379977.8	NP_002180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8	c.545A>T	p.Asn182Ile	missense_variant	Exon 4 of 7	1	NM_002189.4	ENSP00000369312.3

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	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.023	.;T;T;.;.;.;.;.;T;.;.;T;.;T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.52	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.075	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;.;.;.;.
PhyloP100		0.14
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	.;.;N;.;.;N;N;N;.;N;N;.;.;N;N
REVEL	Benign	0.051
Sift	Uncertain	0.0090	.;.;D;.;.;D;T;D;.;D;D;.;.;D;D
Sift4G	Uncertain	0.051	T;D;D;D;D;D;T;T;D;D;D;D;D;.;D
Polyphen		0.0030	.;.;B;.;.;B;.;.;.;.;.;.;.;.;.
Vest4		0.13
MutPred		0.17		.;.;Loss of loop (P = 0.0203);.;.;.;.;.;.;.;Loss of loop (P = 0.0203);.;.;.;.;
MVP		0.33
MPC		0.14
ClinPred		0.086	T
GERP RS		1.1
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.18
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2228059; hg19: chr10-6002368;