Submissions for variant NM_138694.4(PKHD1):c.11174+11A>G

gnomAD frequency: 0.01349  dbSNP: rs115072237

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082519	SCV000114561	benign	not specified	2016-04-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000082519	SCV000315758	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001164889	SCV001327046	benign	Autosomal recessive polycystic kidney disease	2017-04-27	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 rule this variant out of causing disease. Therefore, this variant is classified as benign.
Invitae	RCV001164889	SCV001717839	benign	Autosomal recessive polycystic kidney disease	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001576263	SCV001803415	likely benign	not provided	2018-07-10	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292232	SCV001481063	benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKHD1 c.11174+11A>G variant was identified in 4 of 314 proband chromosomes (frequency: 0.01) from Dutch, Czech and European individuals or families with ARPKD and was identified in 5 of 200 chromosomes from healthy individuals (frequency: 0.025) (Obeidova 2015, Losekoot 2005, Bergmann 2005). The variant was also identified in dbSNP (ID: rs115072237) “With Benign allele”, ClinVar (classified benign by EGL Genetic Diagnostics (Eurofins Clinical Diagnostics) and Prevention Genetics), and RWTH AAachen University ARPKD database (classified as a polymorphism). The variant was also identified in control databases in 3588 of 276422 chromosomes (35 homozygous) at a frequency of 0.01 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 89 of 24012 chromosomes (freq: 0.004), Other in 82 (1 homozygous) of 6432 chromosomes (freq: 0.01), Latino in 281 of 34318 chromosomes (freq: 0.008), European Non-Finnish in 2579 (31 homozygous) of 126206 chromosomes (freq: 0.02), Ashkenazi Jewish in 14 of 10138 chromosomes (freq: 0.001), European Finnish in 318 (2 homozygous) of 25726 chromosomes (freq: 0.01), and South Asian in 225 (1 homozygous) of 30778 chromosomes (freq: 0.007). and was not observed in the East Asian population. 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 a difference in splicing. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000082519	SCV002034073	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000082519	SCV002036659	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001164889	SCV002075492	benign	Autosomal recessive polycystic kidney disease	2017-08-09	no assertion criteria provided	clinical testing