chr10-5953182-AAC-TAT

Variant names:

• chr10-5953182-AAC-TAT
• NM_002189.4:c.715_717delGTTinsATA
• IL15RA p.Val239Ile

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_002189.4(IL15RA):c.715_717delGTTinsATA (p.Val239Ile) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.V239I: Benign (ClinVar VariationId 709069, 2 stars)

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL15RA NM_002189.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940
• 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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002189.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	IL15RA NM_002189.4	MANE Select	c.715_717delGTTinsATA p.Val239Ile	missense	N/A	Prot: NP_002180.1 UniProt:
	IL15RA NM_001256765.1		c.973_975delGTTinsATA p.Val325Ile	missense	N/A	Prot: NP_001243694.1 UniProt:
	IL15RA NM_172200.3		c.616_618delGTTinsATA p.Val206Ile	missense	N/A	Prot: NP_751950.2 UniProt:

IL15RA NM_002189.4

MANE Select

HGVSc / HGVSpc.715_717delGTTinsATAp.Val239Ile

Exon rankN/A

missense

Prot: NP_002180.1UniProt: Q13261-1

IL15RA NM_001256765.1

HGVSc / HGVSpc.973_975delGTTinsATAp.Val325Ile

Exon rankN/A

missense

Prot: NP_001243694.1UniProt: Q13261G8CVM3A0A0A0MS77

IL15RA NM_172200.3

HGVSc / HGVSpc.616_618delGTTinsATAp.Val206Ile

Exon rankN/A

missense

Prot: NP_751950.2UniProt: Q13261-3

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	IL15RA ENST00000379977.8	TSL:1MANE Select	c.715_717delGTTinsATA p.Val239Ile	missense	N/A	Prot: ENSP00000369312.3 UniProt:
	IL15RA ENST00000397248.6	TSL:1	c.973_975delGTTinsATA p.Val325Ile	missense	N/A	Prot: ENSP00000380421.3 UniProt:
	IL15RA ENST00000525219.6	TSL:1	c.607_609delGTTinsATA p.Val203Ile	missense	N/A	Prot: ENSP00000431529.2 UniProt:

IL15RA ENST00000379977.8

TSL:1MANE Select

HGVSc / HGVSpc.715_717delGTTinsATAp.Val239Ile

Exon rankN/A

missense

Prot: ENSP00000369312.3UniProt: Q13261-1

IL15RA ENST00000397248.6

TSL:1

HGVSc / HGVSpc.973_975delGTTinsATAp.Val325Ile

Exon rankN/A

missense

Prot: ENSP00000380421.3UniProt: A0A0A0MS77

IL15RA ENST00000525219.6

TSL:1

HGVSc / HGVSpc.607_609delGTTinsATAp.Val203Ile

Exon rankN/A

missense

Prot: ENSP00000431529.2UniProt: Q13261-10

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	0.94

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr10-5995145;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar