Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SIB Swiss Institute of Bioinformatics | RCV000001903 | SCV003932426 | likely pathogenic | Hypotrichosis 8 | criteria provided, single submitter | curation | This variant is interpreted as likely pathogenic for Woolly hair autosomal recessive 1 with or without hypotrichosis. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1); For recessive disorders, detected in trans with a pathogenic variant (PM3); Well-established functional studies show a deleterious effect (PS3 downgraded to supporting); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3). | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000001903 | SCV005204440 | pathogenic | Hypotrichosis 8 | 2024-06-11 | criteria provided, single submitter | clinical testing | Variant summary: LPAR6 c.565G>A (p.Glu189Lys) results in a conservative amino acid change located in the GPCR, rhodopsin-like, 7TM domain (IPR017452) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 249012 control chromosomes (gnomAD). c.565G>A has been reported in the literature in several homozygous individuals affected with Woolly hair, autosomal recessive, with or without hypotrichosis (examples: Saleh_2021, Shimomura_2008). These data indicate that the variant is very likely to be associated with disease. In vitro functional studies, suggest that the variant may be defective in ligand binding and/or signaling (Yanagida_2023). The following publications have been ascertained in the context of this evaluation (PMID: 36173926, 18461368, 34374989, 18297072). ClinVar contains an entry for this variant (Variation ID: 1829). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000001903 | SCV000022060 | pathogenic | Hypotrichosis 8 | 2008-06-01 | no assertion criteria provided | literature only |