Submissions for variant NM_138694.4(PKHD1):c.10210A>G (p.Ile3404Val)

gnomAD frequency: 0.00056  dbSNP: rs147612089

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000727592	SCV000854839	uncertain significance	not provided	2018-06-26	criteria provided, single submitter	clinical testing
Invitae	RCV000814275	SCV000954677	likely benign	Autosomal recessive polycystic kidney disease	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000727592	SCV001993712	uncertain significance	not provided	2020-10-05	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
Ambry Genetics	RCV002535047	SCV003679800	likely benign	Inborn genetic diseases	2022-11-10	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003953290	SCV004770646	likely benign	PKHD1-related condition	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.	RCV000814275	SCV001453261	uncertain significance	Autosomal recessive polycystic kidney disease	2018-05-17	no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV003151141	SCV003839875	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.10210A>G, in exon 61 that results in an amino acid change, p.Ile3404Val. This sequence change has been described in the gnomAD database with a frequency of 0.16063% in the African/African American subpopulation (dbSNP rs147612089). The p.Ile3404Val change affects a poorly conserved amino acid residue located in a domain of the PKHD1 protein that is not known to be functional. The p.Ile3404Val 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.Ile3404Val change remains unknown at this time.