ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.6332+2T>A

dbSNP: rs1783090781
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV001251457 SCV001427100 uncertain significance Autosomal recessive polycystic kidney disease 2018-05-21 criteria provided, single submitter clinical testing A heterozygous canonical splice-site variant, NM_138694.3(PKHD1):c.6332+2T>A, has been identified in intron 38 of 66 of the PKHD1 gene. The variant is likely to cause a splice defect, resulting in frameshift and likely causing non-sense mediated decay. The nucleotide at this position has very high conservation (Phylop UCSC). This nucleotide substitution is predicted to cause aberrant splicing and may result in a truncated protein; further testing via RNA studies are required to confirm if splicing is altered. The variant is absent in population databases (gnomAD, dbSNP, 1000G), and has not been previously reported in clinical cases. Based on the information available at the time of curation, this variant has been classified as VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with POTENTIAL CLINICAL RELEVANCE.
PreventionGenetics, part of Exact Sciences RCV003399026 SCV004110452 pathogenic PKHD1-related disorder 2023-01-27 criteria provided, single submitter clinical testing The PKHD1 c.6332+2T>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in the compound heterozygous state in an individual with polycystic kidney disease (Patient P002 in Supplemental Table 2, Jayasinghe et al. 2021. PubMed ID: 32939031). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice donor site in PKHD1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics RCV004570644 SCV005056275 pathogenic Polycystic kidney disease 4 2024-03-29 criteria provided, single submitter clinical testing

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