Genetic Variant IL17D:p.Arg80Cys (chr13-20704239-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001385224.1(IL17D):c.238C>T(p.Arg80Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000304 in 1,316,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 26)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

IL17D
NM_001385224.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.168

Variant links:

Genes affected

IL17D (HGNC:5984): (interleukin 17D) The protein encoded by this gene is a cytokine that shares the sequence similarity with IL17. The treatment of endothelial cells with this cytokine has been shown to stimulate the production of other cytokines including IL6, IL8 and CSF2/ GM-CSF. The increased expression of IL8 induced by this cytokine was found to be NF-kappa B-dependent. [provided by RefSeq, Jul 2008]

IL17D links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
IL17D	NM_001385224.1 link	c.238C>T	p.Arg80Cys	missense_variant	Exon 1 of 2	ENST00000682841.1	NP_001372153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL17D	ENST00000682841.1 link	c.238C>T	p.Arg80Cys	missense_variant	Exon 1 of 2		NM_001385224.1	ENSP00000508385.1	Q8TAD2
IL17D	ENST00000304920.3 link	c.238C>T	p.Arg80Cys	missense_variant	Exon 2 of 3	1		ENSP00000302924.3	Q8TAD2
IL17D	ENST00000468605.1 link	n.160C>T		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000480610.1	A0A087WWZ4
IL17D	ENST00000498088.1 link	c.*153C>T		downstream_gene_variant		2		ENSP00000479852.1	A0A087WW17

Frequencies

GnomAD3 genomes

AF:

0.0000207

AC:

AN:

145000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000203

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

GnomAD4 exome

AF:

8.54e-7

AC:

AN:

1170942

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

572420

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000216

GnomAD4 genome

AF:

0.0000207

AC:

AN:

145102

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70752

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238C>T (p.R80C) alteration is located in exon 2 (coding exon 1) of the IL17D gene. This alteration results from a C to T substitution at nucleotide position 238, causing the arginine (R) at amino acid position 80 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

Eigen

Benign

-0.057

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.76

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.6

REVEL

Benign

0.16

Sift

Benign

0.042

Sift4G

Uncertain

0.045

Polyphen

1.0

Vest4

0.11

MutPred

0.77

Loss of MoRF binding (P = 0.0021);

MVP

0.62

MPC

1.6

ClinPred

0.83

GERP RS

1.2

Varity_R

0.14

gMVP

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over