rs1057518744

Variant names:

• chr22-17108516-A-AAGCAGGAGATGGTGGAG
• rs1057518744
• NM_014339.7:c.1302_1318dupGGAGATGGTGGAGAGCA

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Strong PP5

The NM_014339.7(IL17RA):​c.1302_1318dupGGAGATGGTGGAGAGCA​(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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 2 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 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 0.493 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PP5: Variant 22-17108516-A-AAGCAGGAGATGGTGGAG is Pathogenic according to our data. Variant chr22-17108516-A-AAGCAGGAGATGGTGGAG is described in ClinVar as Pathogenic. ClinVar VariationId is 372204.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	NM_014339.7	MANE Select	c.1302_1318dupGGAGATGGTGGAGAGCA	p.Asn440ArgfsTer50	frameshift	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.1200_1216dupGGAGATGGTGGAGAGCA	p.Asn406ArgfsTer50	frameshift	Exon 12 of 12	NP_001276834.1	Q96F46-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	ENST00000319363.11	TSL:1 MANE Select	c.1302_1318dupGGAGATGGTGGAGAGCA	p.Asn440ArgfsTer50	frameshift	Exon 13 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.1290_1306dupGGAGATGGTGGAGAGCA	p.Asn436ArgfsTer50	frameshift	Exon 12 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.1200_1216dupGGAGATGGTGGAGAGCA	p.Asn406ArgfsTer50	frameshift	Exon 12 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Immunodeficiency 51 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=10/190	disease causing (ClinVar)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1057518744;

hg19: chr22-17589406;