rs1057518744

Positions:

• chr22-17108516-A-AAGCAGGAGATGGTGGAG

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_014339.7(IL17RA):​c.1302_1318dup​(p.Asn440ArgfsTer50) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: IL17RA NM_014339.7 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.87

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.501 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 22-17108516-A-AAGCAGGAGATGGTGGAG is Pathogenic according to our data. Variant chr22-17108516-A-AAGCAGGAGATGGTGGAG is described in ClinVar as [Pathogenic]. Clinvar id is 372204.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.1302_1318dup	p.Asn440ArgfsTer50	frameshift_variant	13/13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.1200_1216dup	p.Asn406ArgfsTer50	frameshift_variant	12/12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.1302_1318dup	p.Asn440ArgfsTer50	frameshift_variant	13/13	1	NM_014339.7	ENSP00000320936	P2
IL17RA	ENST00000612619.2	c.1200_1216dup	p.Asn406ArgfsTer50	frameshift_variant	12/12	5		ENSP00000479970	A2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 34

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency 51 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 19, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057518744; hg19: chr22-17589406;