Evidence map›Paper›PMID 30369598›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019

Population data improves variant interpretation in autosomal dominant polycystic kidney disease.

Amali C Mallawaarachchi, Timothy J Furlong, John Shine, Peter C Harris, Mark J Cowley

Open access · bronzeAbstract read
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Observational
  5. An intermediate-effect size variant inProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  6. Article
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Amali C MallawaarachchiDivision of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Timothy J FurlongDivision of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, NSW, Australia.
John ShineDivision of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Peter C HarrisDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Mark J CowleyKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia. m.cowley@garvan.org.au.
Garvan Institute of Medical Research · AUMayo Clinic · US

Funding

Pilot and FeasibilityP30DK090728 · NIDDK · MAYO CLINIC ROCHESTER · PI ROMERO, MICHAEL F. · 2010 to 2019
$11.8M
NIDDK NIH HHS P30 DK090728
6 · The paper itself

Abstract

purposeAutosomal dominant polycystic kidney disease (ADPKD) is a common adult-onset monogenic disorder, with prevalence of 1/1000. Population databases including ExAC have improved pathogenic variant prioritization in many diseases. Due to pseudogene homology of PKD1, the predominant ADPKD disease gene, and the variable disease severity and age of onset, we aimed to investigate the utility of ExAC for variant assessment in ADPKD.

methodsWe assessed coverage and variant quality in the ExAC cohort and combined allele frequency and age data from the ExAC database (n = 60,706) with curated variants from 2000 ADPKD pedigrees (ADPKD Mutation Database).

resultsSeventy-six percent of PKD1 and PKD2 were sequenced adequately for variant discovery and variant quality was high in ExAC. In ExAC, we identified 25 truncating and 393 previously reported disease-causing variants in PKD1 and PKD2, 6.9-fold higher than expected. Fifty-four different variants, previously classified as disease-causing, were observed in ≥5 participants in ExAC.

conclusionOur study demonstrates that many previously implicated disease-causing variants are too common, challenging their pathogenicity, or penetrance. The presence of protein-truncating variants in older participants in ExAC demonstrates the complexity of variant classification and highlights need for further study of prevalence and penetrance of this common monogenic disease.

Indexed as

AllelesCohort StudiesFemaleGene FrequencyGenetics, PopulationGenetic VariationHumansMaleMutationPedigreePolycystic Kidney, Autosomal DominantSequence Analysis, DNATRPP Cation ChannelsTRPP Cation ChannelsADPKDexome sequencingPKD1PKD2variant interpretation

Identifiers

PMID30369598
PMCPMC6677146
OpenAlexW2898450471

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.