Submissions for variant NM_018718.3(CEP41):c.616C>G (p.Pro206Ala)

gnomAD frequency: 0.00218  dbSNP: rs143303575

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000878420	SCV000466825	uncertain significance	Joubert syndrome 15	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001702359	SCV000564864	uncertain significance	not provided	2021-11-16	criteria provided, single submitter	clinical testing	Reported previously as a heterozygous variant in multiple families with autism; however, these individuals were not reported to have any symptoms of JSRD, and a second CEP41 variant was not identified in any of these individuals (Korvatska et al., 2011); Published functional studies suggest a damaging effect (Patowary et al., 2019); 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: 30664616, 21438139)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000878420	SCV001021323	benign	Joubert syndrome 15	2024-01-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001702359	SCV004161074	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	CEP41: BS2
University of Washington Center for Mendelian Genomics, University of Washington	RCV001261666	SCV001438971	likely pathogenic	Familial Autism Spectrum Disorder		no assertion criteria provided	research
Clinical Genetics, Academic Medical Center	RCV000483238	SCV001921969	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702359	SCV001932734	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001702359	SCV001963862	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003922590	SCV004750795	likely benign	CEP41-related disorder	2022-05-12	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).