Genetic Variant IL17D:p.Ala26Val (chr13-20704078-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385224.1(IL17D):c.77C>T(p.Ala26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,118,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A26T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

IL17D
NM_001385224.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.483

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1053409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17D	NM_001385224.1 link	c.77C>T	p.Ala26Val	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.77C>T	p.Ala26Val	missense_variant	Exon 1 of 2		NM_001385224.1	ENSP00000508385.1	Q8TAD2
IL17D	ENST00000304920.3 link	c.77C>T	p.Ala26Val	missense_variant	Exon 2 of 3	1		ENSP00000302924.3	Q8TAD2
IL17D	ENST00000498088.1 link	c.98C>T	p.Ala33Val	missense_variant	Exon 2 of 2	2		ENSP00000479852.1	A0A087WW17
IL17D	ENST00000468605.1 link	n.-2C>T		upstream_gene_variant		3		ENSP00000480610.1	A0A087WWZ4

Frequencies

GnomAD3 genomes

AF:

0.000188

AC:

AN:

143324

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000507

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:

0.000385

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000149

AC:

AN:

6714

Hom.:

AF XY:

0.000217

AC XY:

AN XY:

4610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000319

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000271

AC:

264

AN:

974934

Hom.:

Cov.:

AF XY:

0.000284

AC XY:

132

AN XY:

464354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000206

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:

0.000285

Gnomad4 OTH exome

AF:

0.000538

GnomAD4 genome

AF:

0.000188

AC:

AN:

143324

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

AN XY:

69880

show subpopulations

Gnomad4 AFR

AF:

0.0000507

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000385

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000159

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.77C>T (p.A26V) 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 77, causing the alanine (A) at amino acid position 26 to be replaced by a valine (V). 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

Benign

0.16

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

.;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.43

.;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.072

Sift

Benign

0.30

.;T

Sift4G

Pathogenic

0.0

D;T

Polyphen

0.0010

.;B

Vest4

0.057

MutPred

0.48

.;Loss of relative solvent accessibility (P = 0.0186);

MVP

0.38

MPC

0.58

ClinPred

0.029

GERP RS

1.8

Varity_R

0.075

gMVP

0.36

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