Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001004189 | SCV001163021 | pathogenic | Autosomal recessive polycystic kidney disease | criteria provided, single submitter | clinical testing | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001004189 | SCV001362925 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2021-11-08 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.8935C>T (p.Arg2979X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251132 control chromosomes (gnomAD). c.8935C>T has been reported in the literature in individuals affected with Polycystic Kidney And Hepatic Disease (Denamur_2010, Szabo_2018). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV001004189 | SCV002171774 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-09-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg2979*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is present in population databases (rs765020336, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with polycystic kidney disease (PMID: 19940839, 29956005). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 813373). |
| Victorian Clinical Genetics Services, |
RCV002471011 | SCV002769193 | pathogenic | Polycystic kidney disease 4 | 2020-05-01 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 57 of 67). (P) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (1 heterozygote, 0 homozygotes). (P) 0402 - Variant is located in a gene associated with a severe early onset recessive condition that is intolerant to bi-allelic loss-of-function variants. (P) 0701 - Multiple comparable variants which are also NMD predicted have very strong previous evidence for pathogenicity (ClinVar). (P) 0803 - Low previous evidence of pathogenicity in one unrelated individual (PMID:29956005). (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1205 - Variant is maternally inherited. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |
| Baylor Genetics | RCV002471011 | SCV004204736 | pathogenic | Polycystic kidney disease 4 | 2023-01-23 | criteria provided, single submitter | clinical testing |