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

gnomAD frequency: 0.00048  dbSNP: rs182018947

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145609	SCV000192706	pathogenic	Microcephaly 9, primary, autosomal recessive	2014-07-28	criteria provided, single submitter	clinical testing
Courtagen Diagnostics Laboratory, Courtagen Life Sciences	RCV000145609	SCV000236533	pathogenic	Microcephaly 9, primary, autosomal recessive	2014-01-28	criteria provided, single submitter	clinical testing
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	RCV000490391	SCV000267247	pathogenic	Seckel syndrome 5	2016-03-18	criteria provided, single submitter	reference population
GeneDx	RCV000286958	SCV000329695	pathogenic	not provided	2022-01-26	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: 30833958, 31980526, 25525159, 21131973, 27219052, 34426522)
Fulgent Genetics, Fulgent Genetics	RCV000515277	SCV000611256	pathogenic	Seckel syndrome 5; Microcephaly 9, primary, autosomal recessive	2017-05-18	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000145609	SCV000784549	likely pathogenic	Microcephaly 9, primary, autosomal recessive	2024-05-11	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000286958	SCV000863001	likely pathogenic	not provided	2018-08-15	criteria provided, single submitter	clinical testing
3billion	RCV000145609	SCV002012250	pathogenic	Microcephaly 9, primary, autosomal recessive	2021-10-02	criteria provided, single submitter	clinical testing	Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000295, PM2). The variant was observed in trans with a pathogenic variant (NM_001194998.1:c.314G>A) as compound heterozygous (3billion dataset, PM3).The variant has been reported as pathogenic (ClinVar ID: VCV000158240.10). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Revvity Omics, Revvity	RCV000286958	SCV002017012	pathogenic	not provided	2019-09-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000286958	SCV002822185	pathogenic	not provided	2024-02-01	criteria provided, single submitter	clinical testing	CEP152: PVS1, PM2, PM3
Labcorp Genetics (formerly Invitae), Labcorp	RCV000286958	SCV003281289	pathogenic	not provided	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr678*) in the CEP152 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP152 are known to be pathogenic (PMID: 21131973). This variant is present in population databases (rs182018947, gnomAD 0.1%). This premature translational stop signal has been observed in individual(s) with CEP152-related conditions (PMID: 21131973). ClinVar contains an entry for this variant (Variation ID: 158240). For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV000490391	SCV004171351	pathogenic	Seckel syndrome 5		criteria provided, single submitter	clinical testing	The stop gained c.2034T>G(p.Tyr678Ter) variant in CEP152 gene has been reported previously in compound heterozygous state in individual(s) affected with Seckel syndrome (Kalay E, et. al., 2011; Fujikura K., 2016). The p.Tyr678Ter variant has been reported with allele frequency of 0.03% in gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Signifiance / Likely Pathogenic / Pathogenic (multiple submissions). The nucleotide change c.2034T>G in CEP152 is predicted as conserved by GERP++. This sequence change creates a premature translational stop signal (p.Tyr678Ter) in the CEP152 gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000145609	SCV004806962	pathogenic	Microcephaly 9, primary, autosomal recessive	2024-03-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004019767	SCV004925456	pathogenic	Inborn genetic diseases	2022-01-13	criteria provided, single submitter	clinical testing	The c.2034T>G (p.Y678*) alteration, located in exon 16 (coding exon 15) of the CEP152 gene, consists of a T to G substitution at nucleotide position 2034. This changes the amino acid from a tyrosine (Y) to a stop codon at amino acid position 678. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration has been reported in the compound heterozygous state with a second CEP152 alteration in a patient with clinical features of CEP152-related Seckel syndrome (Kalay, 2011). Based on the available evidence, this alteration is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV004556749	SCV005045613	pathogenic	CEP152-related disorder	2023-05-24	criteria provided, single submitter	clinical testing
OMIM	RCV000490391	SCV000045316	pathogenic	Seckel syndrome 5	2011-01-01	no assertion criteria provided	literature only
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000490391	SCV000784550	uncertain significance	Seckel syndrome 5	2018-03-05	flagged submission	clinical testing