ClinVar Miner

Submissions for variant NM_017563.5(IL17RD):c.572C>T (p.Pro191Leu)

gnomAD frequency: 0.00012  dbSNP: rs200088377
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Chan Lab, Boston Children's Hospital RCV000156942 SCV000206663 likely pathogenic Delayed puberty 2014-11-01 criteria provided, single submitter case-control
Mendelics RCV000987280 SCV001136537 uncertain significance Cerebral arteriovenous malformation 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001850174 SCV002129240 uncertain significance not provided 2021-09-26 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 191 of the IL17RD protein (p.Pro191Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs200088377, ExAC 0.1%). This variant has been observed in individual(s) with idiopathic hypogonadotropic hypogonadism (PMID: 32389901). ClinVar contains an entry for this variant (Variation ID: 180145). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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.
CeGaT Center for Human Genetics Tuebingen RCV001850174 SCV004150362 benign not provided 2022-05-01 criteria provided, single submitter clinical testing IL17RD: BS1, BS2
Genetic Services Laboratory, University of Chicago RCV003150956 SCV003839606 uncertain significance not specified 2022-10-03 no assertion criteria provided clinical testing DNA sequence analysis of the IL17RD gene demonstrated a sequence change, c.572C>T, in exon 6 that results in an amino acid change, p.Pro191Leu. This sequence change has been previously described in a female individual with normosmic isolated hypogonadotropic hypogonadism (PMID: 32389901). This sequence change has been described in the gnomAD database with a frequency of 0.15% in the East Asian subpopulation (dbSNP rs200088377). The p.Pro191Leu change affects a highly conserved amino acid residue located in a domain of the IL17RD protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Pro191Leu substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Pro191Leu change remains unknown at this time.

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