Submissions for variant NM_001194998.2(CEP152):c.2034T>G (p.Tyr678Ter) (rs182018947)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Courtagen Diagnostics Laboratory,Courtagen Life Sciences	RCV000145609	SCV000236533	pathogenic	Primary autosomal recessive microcephaly 9	2014-01-28	criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000286958	SCV000863001	likely pathogenic	not provided	2018-08-15	criteria provided, single submitter	clinical testing
Fulgent Genetics,Fulgent Genetics	RCV000515277	SCV000611256	pathogenic	Seckel syndrome 5; Primary autosomal recessive microcephaly 9	2017-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000286958	SCV000329695	pathogenic	not provided	2015-11-20	criteria provided, single submitter	clinical testing	The Y678X nonsense variant in the CEP152 gene has been reported previously in association with Seckel syndrome in an individual who had a second pathogenic variant on the opposite allele (Kalay et al., 2011). It was not observed with any significant frequency in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The 1000 Genomes Project reports Y678X was observed in 2/198 (1%) alleles from individuals of Kenyan background. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, Y678X is considered a pathogenic variant.
Genetic Services Laboratory, University of Chicago	RCV000145609	SCV000192706	pathogenic	Primary autosomal recessive microcephaly 9	2014-07-28	criteria provided, single submitter	clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences	RCV000145609	SCV000784549	uncertain significance	Primary autosomal recessive microcephaly 9	2018-03-05	criteria provided, single submitter	clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences	RCV000490391	SCV000784550	uncertain significance	Seckel syndrome 5	2018-03-05	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000270590	SCV000392890	uncertain significance	CEP152-Related Disorders	2018-05-14	criteria provided, single submitter	clinical testing	The CEP152 c.2034T>G (p.Tyr678Ter) variant is a stop-gained variant that is predicted to cause premature truncation of the protein. The p.Tyr678Ter variant has been reported in one study in which it was found in a compound heterozygous state with a second null variant in one patient with Seckel syndrome presenting with a severe phenotype (Kalay et al. 2010). The p.Tyr678Ter variant was absent from 550 controls but is reported at a frequency of 0.001761 in the African American population of the Exome Sequencing Project. Due to the potential impact of stop-gained variants and limited evidence, the p.Tyr678Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for CEP152-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM	RCV000490391	SCV000045316	pathogenic	Seckel syndrome 5	2011-01-01	no assertion criteria provided	literature only
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center	RCV000490391	SCV000267247	pathogenic	Seckel syndrome 5	2016-03-18	criteria provided, single submitter	reference population