Submissions for variant NM_138694.4(PKHD1):c.7736C>T (p.Ala2579Val)

gnomAD frequency: 0.00019  dbSNP: rs78361537

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000633430	SCV000754654	uncertain significance	Autosomal recessive polycystic kidney disease	2024-03-20	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2579 of the PKHD1 protein (p.Ala2579Val). This variant is present in population databases (rs78361537, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 528298). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Eurofins Ntd Llc (ga)	RCV000731742	SCV000859591	uncertain significance	not provided	2018-02-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000731742	SCV002558269	uncertain significance	not provided	2022-01-26	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
Fulgent Genetics, Fulgent Genetics	RCV005034207	SCV005671748	likely benign	Polycystic kidney disease 4	2024-03-05	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000633430	SCV002078012	uncertain significance	Autosomal recessive polycystic kidney disease	2017-05-06	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004748870	SCV005360877	uncertain significance	PKHD1-related disorder	2024-04-12	no assertion criteria provided	clinical testing	The PKHD1 c.7736C>T variant is predicted to result in the amino acid substitution p.Ala2579Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.080% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.