chr22-17109306-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_014339.7(IL17RA):c.2087T>G(p.Leu696Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,531,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L696M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

IL17RA
NM_014339.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.12

Publications

1 publications found

Variant links:

Genes affected

IL17RA (HGNC:5985): (interleukin 17 receptor A) Interleukin 17A (IL17A) is a proinflammatory cytokine secreted by activated T-lymphocytes. It is a potent inducer of the maturation of CD34-positive hematopoietic precursors into neutrophils. The transmembrane protein encoded by this gene (interleukin 17A receptor; IL17RA) is a ubiquitous type I membrane glycoprotein that binds with low affinity to interleukin 17A. Interleukin 17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. Like other cytokine receptors, this receptor likely has a multimeric structure. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2014]

IL17RA Gene-Disease associations (from GenCC):

immunodeficiency 51
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
chronic mucocutaneous candidiasis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IL17RA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03976834).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000079 (12/151934) while in subpopulation AFR AF = 0.00029 (12/41398). AF 95% confidence interval is 0.000167. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014339.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	NM_014339.7	MANE Select	c.2087T>G	p.Leu696Arg	missense	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.1985T>G	p.Leu662Arg	missense	Exon 12 of 12	NP_001276834.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	ENST00000319363.11	TSL:1 MANE Select	c.2087T>G	p.Leu696Arg	missense	Exon 13 of 13	ENSP00000320936.6
	IL17RA	ENST00000612619.2	TSL:5	c.1985T>G	p.Leu662Arg	missense	Exon 12 of 12	ENSP00000479970.1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000146

AC:

AN:

137058

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000281

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000435

AC:

AN:

1379534

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680758

show subpopulations

African (AFR)

AF:

0.000190

AC:

AN:

31572

American (AMR)

AF:

0.00

AC:

AN:

36058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23732

East Asian (EAS)

AF:

0.00

AC:

AN:

36094

South Asian (SAS)

AF:

0.00

AC:

AN:

78804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35750

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4922

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1075322

Other (OTH)

AF:

0.00

AC:

AN:

57280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000790

AC:

AN:

151934

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

41398

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67928

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000288

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2087T>G (p.L696R) alteration is located in exon 13 (coding exon 13) of the IL17RA gene. This alteration results from a T to G substitution at nucleotide position 2087, causing the leucine (L) at amino acid position 696 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Immunodeficiency 51

Uncertain:1

Apr 18, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 696 of the IL17RA protein (p.Leu696Arg). This variant is present in population databases (rs753376068, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with IL17RA-related conditions. ClinVar contains an entry for this variant (Variation ID: 542914). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.23

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.66

M_CAP

Benign

0.030

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

1.1

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.042

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.015

Polyphen

0.85

Vest4

0.14

MutPred

0.40

Gain of solvent accessibility (P = 0.0171)

MVP

0.14

MPC

0.65

ClinPred

0.33

GERP RS

0.99

Varity_R

0.26

gMVP

0.63

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over