Submissions for variant NM_014956.5(CEP164):c.3055C>T (p.Gln1019Ter)

gnomAD frequency: 0.00004  dbSNP: rs746453731

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001879106	SCV002145420	pathogenic	Nephronophthisis 15	2023-04-18	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1371663). This variant has not been reported in the literature in individuals affected with CEP164-related conditions. This variant is present in population databases (rs746453731, gnomAD 0.005%). This sequence change creates a premature translational stop signal (p.Gln1019*) in the CEP164 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP164 are known to be pathogenic (PMID: 22863007, 28125082, 32367404, 34132027, 34499853).
GeneDx	RCV003154207	SCV003842528	pathogenic	not provided	2023-03-03	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34132027)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001879106	SCV004121905	pathogenic	Nephronophthisis 15	2023-10-19	criteria provided, single submitter	clinical testing	Variant summary: CEP164 c.3055C>T (p.Gln1019X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.2e-05 in 250662 control chromosomes (gnomAD). c.3055C>T has been reported in the literature in an individual affected with ciliopathy-spectrum disease (e.g. Strong_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34132027). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.