Submissions for variant NM_014956.5(CEP164):c.1220C>T (p.Ser407Phe)

gnomAD frequency: 0.00084  dbSNP: rs150314805

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001071532	SCV001236840	uncertain significance	Nephronophthisis 15	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 407 of the CEP164 protein (p.Ser407Phe). This variant is present in population databases (rs150314805, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. 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: 864363). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
GeneDx	RCV001540314	SCV001758187	uncertain significance	not provided	2023-06-12	criteria provided, single submitter	clinical testing	Identified in a patient with personal and family history of pancreatic cancer, however, additional clinical history and familial segregation information were not included (Smith et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 26546047)
Fulgent Genetics, Fulgent Genetics	RCV001071532	SCV002793884	uncertain significance	Nephronophthisis 15	2022-05-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001540314	SCV004136141	likely benign	not provided	2022-03-01	criteria provided, single submitter	clinical testing	CEP164: BP4
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004813720	SCV005072928	uncertain significance	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003938434	SCV004752501	likely benign	CEP164-related disorder	2020-03-28	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).