Submissions for variant NM_001009944.3(PKD1):c.5763G>A (p.Leu1921=)

gnomAD frequency: 0.03243  dbSNP: rs2575313

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000253176	SCV000305756	benign	not specified		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000999800	SCV000604780	benign	Polycystic kidney disease, adult type	2020-02-20	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000712634	SCV000843151	benign	not provided	2018-01-26	criteria provided, single submitter	clinical testing
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research	RCV001254197	SCV001430218	benign	Autosomal dominant polycystic kidney disease	2019-01-01	criteria provided, single submitter	research
GeneDx	RCV000712634	SCV001945369	benign	not provided	2019-10-03	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001291914	SCV000592786	benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Leu1921Leu variant was identified in 39 of 842 proband chromosomes (frequency: 0.046) from individuals or families with ADPKD or renal disease, and was not identified in 100 control chromosomes from healthy individuals (Bataille 2011, Garcia-Gonzalez 2007, McCluskey 2002, Rossetti 2012, Thomas 1999). All the above studies have identified the variant as a polymorphism. The p.Leu1921Leu variant was identified in the dbSNP (ID: rs2575313) with unknown clinical significance with a minor allele frequency 0.012 (60 of 5000 chromosomes in 1000 Genome Project). In the NHLBI Exome Sequencing Project (Exome Variant Server), the variant was identified in 387 of 8262 alleles (frequency: 0.05) in the European Americans and 39 of 4067 alleles in African Americans (Frequency: 0.01). The variant was identified in the Exome Aggregation Consortium database (March 14, 2016) in 3512 of 107304 chromosomes (frequency: 0.03) or 471 of 5522 of European (Finnish), 2749 of 58470 European (Non-Finnish), 151 of 10988 Latino, 61 of 7502 African, and 59 of 15918 South Asians chromosomes and was not found in East Asians. The variant was identified in the PKD Mutation Database and classified as likely neutral. The c.5763G>A 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 greater than 10% difference in splicing. The p.Leu1921Leu 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 summary, based on the above information, this variant meets our laboratory criteria to be classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000253176	SCV002036433	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000253176	SCV002037373	benign	not specified		no assertion criteria provided	clinical testing