ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.7734-6C>A

gnomAD frequency: 0.00020  dbSNP: rs367564272
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000591197 SCV000709595 uncertain significance not provided 2017-06-26 criteria provided, single submitter clinical testing
Invitae RCV001088505 SCV001014131 likely benign Autosomal recessive polycystic kidney disease 2024-01-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174777 SCV001338106 uncertain significance not specified 2020-01-23 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.7734-6C>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 2/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 7.1e-05 in 282508 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease (7.1e-05 vs 0.0071), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.7734-6C>A in individuals affected with Polycystic Kidney and Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (1x) and likely benign (1x). Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV000591197 SCV002001154 uncertain significance not provided 2020-06-29 criteria provided, single submitter clinical testing In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge

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