ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2269A>C (p.Ile757Leu) (rs777183511)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000288236 SCV000345649 uncertain significance not provided 2016-08-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000317551 SCV000464106 uncertain significance Autosomal recessive polycystic kidney disease 2016-07-27 criteria provided, single submitter clinical testing The PKHD1 c.2269A>C (p.Ile757Leu) variant is a missense variant that has been reported in two studies, where it was found in a compound heterozygous state in two individuals with polycystic kidney disease (Rossetti et al. 2003; Sharp et al. 2005). This variant was absent from 300 control chromosomes. It is reported at a frequency of 0.00017 in the Latino population of the Exome Aggregation Consortium, but this frequency is based on two alleles only in a region of good sequencing coverage. Therefore, the variant is presumed to be rare. The evidence for this variant is limited. The p.Ile757Leu variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive polycystic kidney disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
SIB Swiss Institute of Bioinformatics RCV000317551 SCV000803597 uncertain significance Autosomal recessive polycystic kidney disease 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Uncertain Significance - Conflicting Evidence, for Polycystic kidney disease 4 with or without polycystic liver disease, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.

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