Submissions for variant NM_001009944.3(PKD1):c.3183G>A (p.Glu1061=)

gnomAD frequency: 0.00165  dbSNP: rs148727945

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000245641	SCV000305720	likely benign	not specified		criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000992573	SCV001144972	benign	not provided	2019-01-24	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001285327	SCV001471740	likely benign	Polycystic kidney disease, adult type	2020-02-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000992573	SCV001812190	likely benign	not provided	2020-10-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001285327	SCV002806441	benign	Polycystic kidney disease, adult type	2021-07-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000992573	SCV005433435	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	PKD1: BP4, BP7, BS2
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001291870	SCV000592757	benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Glu1061Glu variant was identified in 1 of 164 proband chromosomes (frequency: 0.006) from individuals or families with clinical features of polycystic renal disease (Garcia-Gonzalez 2007). The variant was also identified in dbSNP (ID: rs148727945) as “NA”, in the ADPKD Mutation Database (classification “likely neutral”), but was not in Clinvitae, ClinVar , GeneInsight COGR, PKD1-LOVD, and PKD1-LOVD 3.0. This variant was identified in the 1000 Genomes Project in 5 of 5000 chromosomes (frequency: 0.001), HAPMAP-EUR in 5 of 1006 chromosomes (frequency: 0.005), NHLBI GO Exome Sequencing Project in 10 of 4570 European American alleles and in 2 of 2590 African American alleles, and in the Exome Aggregation Consortium database (March 14, 2016) in 84 of 43768 alleles, specifically in 68 of 22746 alleles (1 homozygous, frequency: 0.0030) from a population of European (Non-Finnish) individuals, in 14 of 3386 alleles (frequency: 0.0041) from a Latino population, and in 2 of 2432 alleles (frequency: 0.0008) from an African population. The variant was not seen in East Asian, South Asian, or European (Finnish) populations. The p.Glu1061Glu 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. This variant was identified in our laboratory in one individual with ADPKD and a co-occurring pathogenic variant in PKD1 (c.160_166dup, p.Leu56ProfsX60), increasing the likelihood this variant does not have clinical significance. 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)	RCV000992573	SCV002035498	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000992573	SCV002038390	likely benign	not provided		no assertion criteria provided	clinical testing