Submissions for variant NM_001009944.3(PKD1):c.11870G>A (p.Gly3957Asp)

gnomAD frequency: 0.00026  dbSNP: rs536586062

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001195921	SCV001366345	uncertain significance	Polycystic kidney disease, adult type	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001195921	SCV001471235	uncertain significance	Polycystic kidney disease, adult type	2019-08-15	criteria provided, single submitter	clinical testing	The PKD1 c.11870G>A; p.Gly3957Asp variant (rs536586062) is reported in the literature as likely neutral in at least one individual affected with polycystic kidney disease who also carried other rare PKD1 variants (Eisenberger 2015). This variant is found in the general population with an overall allele frequency of 0.056% (90/159624 alleles) in the Genome Aggregation Database. The glycine at codon 3957 is weakly conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: possibly damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Gly3957Asp variant is uncertain at this time. References: Eisenberger T et al. An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease. PLoS One. 2015 Feb 3;10(2):e0116680.
Ambry Genetics	RCV002560211	SCV003682099	uncertain significance	Inborn genetic diseases	2021-08-17	criteria provided, single submitter	clinical testing	The c.11867G>A (p.G3956D) alteration is located in exon 43 (coding exon 43) of the PKD1 gene. This alteration results from a G to A substitution at nucleotide position 11867, causing the glycine (G) at amino acid position 3956 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003928780	SCV004750338	likely benign	PKD1-related condition	2023-02-27	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).