Submissions for variant NM_138694.4(PKHD1):c.7587G>A (p.Gly2529=)

gnomAD frequency: 0.49949  dbSNP: rs12210295

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082571	SCV000114613	benign	not specified	2015-10-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000082571	SCV000315827	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000273935	SCV000464062	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589950	SCV000699876	benign	not provided	2016-07-11	criteria provided, single submitter	clinical testing	Variant summary: The c.7587G>A (p.Gly2529=) in PKHD1 gene is a synonymous change that involves a non-conserved nucleotide with 4/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.506 (61140/120660 chrs tested) including numerous homozygous occurrences. This frequency greatly exceeds the maximal expected frequency of a pathogenic allele (0.007) in this gene. The variant of interest was cited as Benign by a reputable clinical laboratory. It is widely accepted as a rare polymorphism in the field. Taking together, the variant was classified as Benign.
Invitae	RCV000273935	SCV001000019	benign	Autosomal recessive polycystic kidney disease	2024-02-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV001530417	SCV001745238	benign	Polycystic kidney disease 4	2021-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000589950	SCV001874526	benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001530417	SCV002029993	benign	Polycystic kidney disease 4	2021-09-05	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001291887	SCV000592900	benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The c.7587G>A, p.Gly2529Gly variant was identified in 50.67% of 61140 control alleles in the Exome Aggregation Consortium (March 14, 2016). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015).
Natera, Inc.	RCV000273935	SCV002078020	benign	Autosomal recessive polycystic kidney disease	2017-05-11	no assertion criteria provided	clinical testing