NM_017563.5:c.2209G>A

Variant names:

• chr3-57096404-C-T
• rs1024143653
• NM_017563.5:c.2209G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_017563.5(IL17RD):​c.2209G>A​(p.Ala737Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,611,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: IL17RD NM_017563.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

Genes affected

IL17RD (HGNC:17616): (interleukin 17 receptor D) This gene encodes a membrane protein belonging to the interleukin-17 receptor (IL-17R) protein family. The encoded protein is a component of the interleukin-17 receptor signaling complex, and the interaction between this protein and IL-17R does not require the interleukin. The gene product also affects fibroblast growth factor signaling, inhibiting or stimulating growth through MAPK/ERK signaling. Alternate splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2819085).
• BS2: High AC in GnomAdExome4 at 20 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RD	NM_017563.5	c.2209G>A	p.Ala737Thr	missense_variant	Exon 13 of 13	ENST00000296318.12	NP_060033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RD	ENST00000296318.12	c.2209G>A	p.Ala737Thr	missense_variant	Exon 13 of 13	1	NM_017563.5	ENSP00000296318.7
IL17RD	ENST00000320057.9	c.1777G>A	p.Ala593Thr	missense_variant	Exon 14 of 14	1		ENSP00000322250.5
IL17RD	ENST00000463523.5	c.1777G>A	p.Ala593Thr	missense_variant	Exon 13 of 13	1		ENSP00000417516.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251160 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00000881

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1459688 Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8 AN XY: 726342

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.0000135

Gnomad4 OTH exome AF: 0.0000663

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74322

Gnomad4 AFR AF: 0.00

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: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 737 of the IL17RD protein (p.Ala737Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with IL17RD-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.085	T;.;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	T;.;.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	L;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.060	N;N;N;.
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D;D;D;.
Sift4G	Uncertain	0.012	D;D;D;.
Polyphen		1.0	D;.;.;.
Vest4		0.33
MutPred		0.27		Gain of relative solvent accessibility (P = 0.0479);.;.;.;
MVP		0.66
MPC		0.43
ClinPred		0.47	T
GERP RS		5.8
Varity_R		0.058
gMVP		0.38

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

Other links and lift over

dbSNP: rs1024143653; hg19: chr3-57130432; COSMIC: COSV56341122; COSMIC: COSV56341122;