Submissions for variant NM_138694.4(PKHD1):c.10859G>A (p.Arg3620His)

gnomAD frequency: 0.00054  dbSNP: rs149163661

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000595376	SCV000700492	uncertain significance	not provided	2018-06-26	criteria provided, single submitter	clinical testing
Invitae	RCV000816584	SCV000957101	likely benign	Autosomal recessive polycystic kidney disease	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002532360	SCV003680011	uncertain significance	Inborn genetic diseases	2022-11-10	criteria provided, single submitter	clinical testing	The c.10859G>A (p.R3620H) alteration is located in exon 61 (coding exon 60) of the PKHD1 gene. This alteration results from a G to A substitution at nucleotide position 10859, causing the arginine (R) at amino acid position 3620 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV000595376	SCV003761867	uncertain significance	not provided	2023-01-17	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV003925761	SCV004744302	likely benign	PKHD1-related disorder	2022-04-12	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).
Natera, Inc.	RCV000816584	SCV001453255	uncertain significance	Autosomal recessive polycystic kidney disease	2017-11-21	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000595376	SCV001797504	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000595376	SCV001970186	likely benign	not provided		no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV003151109	SCV003839876	uncertain significance	not specified	2022-08-26	no assertion criteria provided	clinical testing	DNA sequence analysis of the PKHD1 gene demonstrated a sequence change, c.10859G>A, in exon 61 that results in an amino acid change, p.Arg3620His. This sequence change has been described in the gnomAD database with a frequency of 0.16% in the African/African American subpopulation (dbSNP rs149163661). The p.Arg3620His change affects a moderately conserved amino acid residue located in a domain of the PKHD1 protein that is not known to be functional. The p.Arg3620His substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with PKHD1-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Arg3620His change remains unknown at this time.