ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2280-2A>G

dbSNP: rs780675990
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001245610 SCV001418908 likely pathogenic Autosomal recessive polycystic kidney disease 2023-04-07 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. ClinVar contains an entry for this variant (Variation ID: 970098). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. This variant is present in population databases (rs780675990, gnomAD 0.0009%). This sequence change affects an acceptor splice site in intron 22 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 RCV003399012 SCV004110448 likely pathogenic PKHD1-related condition 2023-07-18 criteria provided, single submitter clinical testing The PKHD1 c.2280-2A>G variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51913419-T-C). Variants that disrupt the consensus splice acceptor site in PKHD1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Natera, Inc. RCV001245610 SCV002081036 likely pathogenic Autosomal recessive polycystic kidney disease 2017-11-07 no assertion criteria provided clinical testing

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