Submissions for variant NM_001009944.3(PKD1):c.6078C>T (p.Val2026=)

gnomAD frequency: 0.00047  dbSNP: rs147253810

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000250453	SCV000305761	likely benign	not specified		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756507	SCV000884339	benign	Polycystic kidney disease, adult type	2018-12-19	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000250453	SCV001879446	benign	not specified	2021-05-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003456387	SCV004184515	benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	PKD1: BP4, BP7, BS1, BS2
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001291915	SCV000592787	benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Val2026Val variant was identified as a polymorphism in 1 of 164 proband chromosomes (frequency: 0.006) from individuals or families with ADPKD (Garcia-Gonzalez 2007). The variant was also identified in dbSNP (ID: rs147253810) as “NA”, with a minor allele frequency of 0.0016 (8 of 5000 chromosomes) in the 1000 Genome Project; the NHLBI GO Exome Sequencing Project in 8 of 8572 European American chromosomes, the Exome Aggregation Consortium database (March 14, 2016) in 245 (3 homozygous) of 114048 chromosomes (freq. 0.002148) in the following populations: South Asian in 199 of 16220 chromosomes (freq. 0.01227), European (Non-Finnish) in 42 of 61954 chromosomes (freq. 0.0006779), Latino in 2 of 11342 chromosomes (freq. 0.0001763), African in 1 of 8888 chromosomes (freq. 0.0001125), and other in 1 of 840 chromosomes (freq. 0.00119), but was not seen in East Asian and Finnish populations, increasing the likelihood this could be a low frequency benign variant. In addition we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The variant was identified in GeneInsight COGR (as benign) and the ADPKD Mutation Database (as likely neutral). The p.Val2026Val variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 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, this variant is classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000250453	SCV001929776	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000250453	SCV001976206	benign	not specified		no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000250453	SCV003839843	benign	not specified	2022-12-19	no assertion criteria provided	clinical testing