Submissions for variant NM_138694.4(PKHD1):c.11310+1G>C

dbSNP: rs1365407882

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002031165	SCV002317002	likely pathogenic	Autosomal recessive polycystic kidney disease	2021-08-18	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 62 of the PKHD1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839).
PreventionGenetics, part of Exact Sciences	RCV003408098	SCV004108942	pathogenic	PKHD1-related disorder	2023-10-12	criteria provided, single submitter	clinical testing	The PKHD1 c.11310+1G>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or 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	RCV003464400	SCV004204793	likely pathogenic	Polycystic kidney disease 4	2022-05-30	criteria provided, single submitter	clinical testing