Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000867555 | SCV001008796 | likely benign | Autosomal recessive polycystic kidney disease | 2024-01-24 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001358162 | SCV001553828 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The PKHD1 c.11175-10T>G variant was not identified in the literature nor was it identified in ClinVar, LOVD 3.0 or the RWTH AAachen University ARPKD database. The associated condition is Polycystic kidney disease 4, with or without hepatic disease, inherited in an autosomal recessive manner. The variant was identified in dbSNP (ID: rs373424543) and in control databases in 27 of 281438 chromosomes at a frequency of 0.000096 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 4 of 7170 chromosomes (freq: 0.000558), European (non-Finnish) in 22 of 128538 chromosomes (freq: 0.000171) and European (Finnish) in 1 of 24652 chromosomes (freq: 0.000041); it was not observed in the African, Latino, Ashkenazi Jewish, East Asian and South Asian populations. The variant occurs outside of the splicing consensus sequence however 4 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing and the creation of a new 3' splice site at the location of the variant (c.11175-10). However, this information is not predictive enough to assume pathogenicity. Further, MutationTaster classifies the variant as a polymorphism. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |