Submissions for variant NM_007186.6(CEP250):c.1826C>T (p.Ala609Val)

gnomAD frequency: 0.00020  dbSNP: rs145878385

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001065133	SCV001230075	uncertain significance	not provided	2022-10-04	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 609 of the CEP250 protein (p.Ala609Val). This variant is present in population databases (rs145878385, gnomAD 0.2%). This missense change has been observed in individual(s) with clinical features of retinitis pigmentosa (PMID: 28005958). ClinVar contains an entry for this variant (Variation ID: 859101). 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). Experimental studies have shown that this missense change affects CEP250 function (PMID: 28005958). 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.
SIB Swiss Institute of Bioinformatics	RCV001089881	SCV001245377	uncertain significance	Retinal dystrophy	2020-02-14	criteria provided, single submitter	curation	This variant is interpreted as a variant of uncertain significance for retinal dystrophy, autosomal recessive. The following ACMG Tag(s) were applied: PP1, PS3-supporting.
Breakthrough Genomics, Breakthrough Genomics	RCV001065133	SCV005194962	uncertain significance	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004753199	SCV005366581	likely benign	CEP250-related disorder	2024-07-15	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).