Submissions for variant NM_014956.5(CEP164):c.2662C>G (p.Leu888Val)

gnomAD frequency: 0.00056  dbSNP: rs142044303

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484217	SCV000569997	uncertain significance	not provided	2016-04-15	criteria provided, single submitter	clinical testing	The L888V variant in the CEP164 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L888V variant was not observed with a significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L888V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L888V as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001071865	SCV001237195	uncertain significance	Nephronophthisis 15	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 888 of the CEP164 protein (p.Leu888Val). This variant is present in population databases (rs142044303, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with CEP164-related conditions. ClinVar contains an entry for this variant (Variation ID: 420952). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CEP164 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.
Fulgent Genetics, Fulgent Genetics	RCV001071865	SCV002777346	uncertain significance	Nephronophthisis 15	2024-05-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004752910	SCV005361206	likely benign	CEP164-related disorder	2024-09-01	no assertion criteria provided	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).