Submissions for variant NM_001009944.3(PKD1):c.9957C>T (p.Ser3319=)

gnomAD frequency: 0.00388  dbSNP: rs141101590

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000253550	SCV000305822	benign	not specified		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000999816	SCV000604782	benign	Polycystic kidney disease, adult type	2019-05-03	criteria provided, single submitter	clinical testing
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research	RCV001254306	SCV001430258	benign	Autosomal dominant polycystic kidney disease	2019-01-01	criteria provided, single submitter	research
GeneDx	RCV001700019	SCV001982733	likely benign	not provided	2021-03-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22383692, 11967008)
Fulgent Genetics, Fulgent Genetics	RCV000999816	SCV002808399	benign	Polycystic kidney disease, adult type	2021-07-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001700019	SCV004129918	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	PKD1: BP4, BP7
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001291922	SCV000592839	likely benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Ser3319Ser variant was identified in an NGS validation study and in a PHPLC validation study in 4 of 550 proband chromosomes (frequency: 0.007) from individuals or families with ADPKD (Rossetti 2012, Rossetti 2002). The variant was also identified in dbSNP (ID: rs141101590) classified as “NA”. The variant was identified in the PKD Mutation Database classified as "likely neutral". This variant was identified in the 1000 Genomes Project in 10 of 5000 chromosomes (frequency: 0.002); HAPMAP-EUR in 5 of 1006 chromosomes (frequency: 0.005); HAPMAP-AMR in 5 of 694 chromosomes (frequency: 0.007); NHLBI GO Exome Sequencing Project (ESP) in 9 of 6278 (frequency 0.0014) in European American alleles and in 10 of 5000 (frequency 0.0006) African American alleles; and in the Exome Aggregation Consortium (ExAC) database (March 14, 20165) in 41 of 14290 alleles (frequency 0.003) increasing the likelihood this could be a low frequency benign variant. The variant was not identified in Clinvitae, ClinVar, COGR GeneInsight, MutDB, PKD1-LOVD, and PKD1-LOVD 3.0. The p.Ser3319Ser 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 meets our laboratory criteria to be classified as likely benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001700019	SCV001926346	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001700019	SCV001970055	likely benign	not provided		no assertion criteria provided	clinical testing