Submissions for variant NM_138694.4(PKHD1):c.5725C>T (p.Arg1909Trp)

gnomAD frequency: 0.00551  dbSNP: rs115338476

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082561	SCV000114603	benign	not specified	2013-04-15	criteria provided, single submitter	clinical testing
Counsyl	RCV000169055	SCV000220215	likely benign	Autosomal recessive polycystic kidney disease	2014-04-09	criteria provided, single submitter	literature only
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224204	SCV000281597	likely benign	not provided	2015-10-29	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Invitae	RCV000169055	SCV000291336	benign	Autosomal recessive polycystic kidney disease	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000082561	SCV000315814	benign	not specified		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000082561	SCV000699868	benign	not specified	2022-02-25	criteria provided, single submitter	clinical testing	Variant summary: PKHD1 c.5725C>T (p.Arg1909Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 251488 control chromosomes, predominantly at a frequency of 0.019 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in PKHD1 causing Polycystic Kidney And Hepatic Disease phenotype (0.0071), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as benign (n=2) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as benign.
Illumina Laboratory Services, Illumina	RCV000169055	SCV001323631	likely benign	Autosomal recessive polycystic kidney disease	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV000224204	SCV001916070	benign	not provided	2020-04-01	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27401137, 27843768, 15805161)
Fulgent Genetics, Fulgent Genetics	RCV002498434	SCV002808911	likely benign	Polycystic kidney disease 4	2022-04-10	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000169055	SCV002078070	benign	Autosomal recessive polycystic kidney disease	2017-06-30	no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000082561	SCV003839872	benign	not specified	2022-09-13	no assertion criteria provided	clinical testing