Submissions for variant NM_138694.4(PKHD1):c.5236+14A>G

gnomAD frequency: 0.01912  dbSNP: rs12210725

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082555	SCV000114597	benign	not specified	2016-02-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000082555	SCV000315810	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000323267	SCV000464083	benign	Autosomal recessive polycystic kidney disease	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Counsyl	RCV000323267	SCV000789977	benign	Autosomal recessive polycystic kidney disease	2017-04-26	criteria provided, single submitter	clinical testing
Invitae	RCV000323267	SCV001725675	benign	Autosomal recessive polycystic kidney disease	2024-02-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV001530434	SCV001745262	benign	Polycystic kidney disease 4	2021-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001711263	SCV001943390	benign	not provided	2018-07-10	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001291852	SCV000592895	benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKHD1 c.5236+14A>G variant was identified as a polymorphism both in proband and control chromosomes at a frequency: 0.05 (Bergmann 2005 , Losekoot 2005 , Sharp 2005 ). The variant was also identified in dbSNP (ID: rs12210725) “With Benign allele”, with a minor allele frequency of 0.0228 (114 of 5000 chromosomes) 1000 Genomes Project; HAPMAP-CEU in 4 of 120 chromosomes (frequency: 0.3333); HAPMAP-HCB in 2 of 90 chromosomes (frequency: 0.02222); NHLBI GO Exome Sequencing Project in 281 of 8600 European American (freq. 0.0327) and 21 of 4406 (freq. 0.004766) African American chromosomes; Exome Aggregation Consortium database (March 14, 2016) in 3671 (93 homozygous) of 117172 chromosomes (freq. 0.03133) in the following populations: South Asian in 1393 of 16478 chromosomes (freq. 0.08454), European (Non-Finnish) in 1975 of 64092 chromosomes (freq. 0.03082), Latino in 136 of 11480 chromosomes (freq. 0.01185), European (Finnish) in 54 of 6600 chromosomes (freq. 0.008182), and African in 45 of 9138 chromosomes (freq. 0.004924), East Asian in 42 of 8498 (freq. 0.004942) and Other populations in 26 of 886 (freq. 0.02935), indicating the variant a benign polymorphism; Clinvitae (benign by EmyClass); the ClinVar (benign by Emory Genetics), GeneInsight COGR (benign by LMM); RWTH AAachen University ARPKD database (polymorphism). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict the abolishment of the consensus splice site but predict creation of a new 5' splice site in this region. This information is not very predictive of pathogenicity. 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)	RCV000082555	SCV001798741	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000082555	SCV001929992	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000323267	SCV002078085	benign	Autosomal recessive polycystic kidney disease	2018-04-13	no assertion criteria provided	clinical testing