Submissions for variant NM_138694.4(PKHD1):c.9237G>A (p.Ala3079=)

gnomAD frequency: 0.30589  dbSNP: rs765525

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082591	SCV000114633	benign	not specified	2015-10-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000082591	SCV000315852	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000351510	SCV000464046	benign	Autosomal recessive polycystic kidney disease	2018-01-13	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.
Invitae	RCV000351510	SCV001000018	benign	Autosomal recessive polycystic kidney disease	2024-02-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV001530472	SCV001745310	benign	Polycystic kidney disease 4	2021-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001705804	SCV001830339	benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001530472	SCV002029985	benign	Polycystic kidney disease 4	2021-09-05	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001027933	SCV000592906	benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKHD1 p.Ala3079= variant was identified in dbSNP (ID: rs765525) “With Benign allele”, ClinVar (classified benign by EGL Genetic Diagnostics (Eurofins Clinical Diagnostics), Prevention Genetics, Illumina), Clinvitae (3x), RWTH AAachen University ARPKD database (as a polymorphism) and in control databases in 113331 (26391 homozygous) of 276718 chromosomes at a frequency of 0.4 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 2095 (96 homozygous) of 24010 chromosomes (freq: 0.09), Other in 2490 (481 homozygous) of 6458 chromosomes (freq: 0.4), Latino in 19685 (5835 homozygous) of 34372 chromosomes (freq: 0.6), European Non-Finnish in 46358 (8579 homozygous) of 126354 chromosomes (freq: 0.4), Ashkenazi Jewish in 3338 (532 homozygous) of 10138 chromosomes (freq: 0.3), East Asian in 13406 (4748 homozygous) of 18840 chromosomes (freq: 0.7), European Finnish in 10817 (2293 homozygous) of 25772 chromosomes (freq: 0.4), and South Asian in 15142 (3827 homozygous) of 30774 chromosomes (freq: 0.5). The variant was not identified in the GeneInsight-COGR, or LOVD 3.0. The p.Ala3079= 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 benign.
Natera, Inc.	RCV001027933	SCV001190663	benign	Polycystic kidney disease	2019-05-20	no assertion criteria provided	clinical testing