ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.7430G>A (p.Arg2477His) (rs556618384)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000989451 SCV001139781 uncertain significance Polycystic kidney disease, adult type 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000989451 SCV001159941 likely benign Polycystic kidney disease, adult type 2019-01-29 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001292525 SCV001480683 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Arg2477His variant was identified in 1 of 92 proband chromosomes (frequency: 0.01) from Taiwanese individuals or families with ADPKD and was present in 7 of 131 control chromosomes (frequency: 0.05) from healthy individuals (Chang 2013). In this study, 1 family carried two PKD1 likely hypomorphic alleles (p.Arg2477His and p.Arg3439Trp) and both were incompletely penetrant, segregating with mild disease when present alone and severe disease when they occurred simultaneously. The variant was also identified in the following database: dbSNP (ID: rs556618384), ADPKD Mutation Database (as likely neutral), and in control databases in 125 (1 homozygous) of 211962 chromosomes (frequency: 0.0006) increasing the likelihood this could be a low frequency variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following by populations: African in 1 of 18334 chromosomes (freq: 0.00006), Other in 2 of 5342 chromosomes (freq: 0.0004), Latino in 6 of 29510 chromosomes (freq: 0.0002), European Non-Finnish in 6 of 94530 chromosomes (freq: 0.00006), East Asian in 108 (1 homozygous) of 15324 chromosomes (freq: 0.007), and South Asian in 2 of 26416 chromosomes (freq: 0.00008); it was not observed in the Ashkenazi Jewish, or European Finnish populations. The variant was not identified in ClinVar, Clinvitae, Genesight-COGR, and PKD1-LOVD (unavailable) databases. The p.Arg2477 residue is conserved in mammals but not in more distantly related organisms however computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.