Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169512 | SCV000220981 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2014-12-22 | criteria provided, single submitter | literature only | |
| Baylor Genetics | RCV000169512 | SCV001163062 | pathogenic | Autosomal recessive polycystic kidney disease | criteria provided, single submitter | clinical testing | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169512 | SCV001364038 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-01-16 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.1830T>A (p.Tyr610X) 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 1.2e-05 in 251032 control chromosomes (gnomAD). c.1830T>A has been reported in the literature in individuals affected with Polycystic Kidney and Hepatic Disease (examples: Denamur_2010, Shuster_2019). 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. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV000169512 | SCV001584166 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-11-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr610*) 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 (rs749293235, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with PKHD1-related conditions (PMID: 19940839, 30650191). ClinVar contains an entry for this variant (Variation ID: 189100). For these reasons, this variant has been classified as Pathogenic. |
| Laboratory for Molecular Medicine, |
RCV000169512 | SCV001653108 | pathogenic | Autosomal recessive polycystic kidney disease | 2020-06-05 | criteria provided, single submitter | clinical testing | The p.Tyr610X variant in PKHD1 has been reported in the compound heterozygous state in at least one individual with polycystic kidney disease (Denamur 2010 PMID:19940839). It has also been identified in 0.003% (3/113450) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID 189100). This nonsense variant leads to a premature termination codon at position 610, which is predicted to lead to a truncated or absent protein. Loss of function of the PKHD1 gene is an established disease mechanism in autosomal recessive polycystic kidney disease (PKD). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive PKD. ACMG/AMP Criteria applied: PVS1, PM3, PM2. |
| 3billion | RCV003152689 | SCV003841668 | pathogenic | Polycystic kidney disease 4 | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000189100 / PMID: 19940839). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
| Baylor Genetics | RCV003152689 | SCV004204764 | pathogenic | Polycystic kidney disease 4 | 2022-10-17 | criteria provided, single submitter | clinical testing |