NM_001194998.2(CEP152):c.2034T>G (p.Tyr678Ter) AND Seckel syndrome 5

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Mar 18, 2016
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000490391.13

Allele description [Variation Report for NM_001194998.2(CEP152):c.2034T>G (p.Tyr678Ter)]

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

Gene:

CEP152:centrosomal protein 152 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

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

HGVS:

NC_000015.10:g.48767448A>C
NG_027518.2:g.48699T>G
NM_001194998.2:c.2034T>GMANE SELECT
NM_014985.4:c.2034T>G
NP_001181927.1:p.Tyr678Ter
NP_055800.2:p.Tyr678Ter
NC_000015.9:g.49059645A>C
NG_027518.1:g.48699T>G
NM_001194998.1:c.2034T>G
NM_001194998.2:c.2034T>G
NM_014985.3:c.2034T>G

Protein change:

Y678*; TYR678TER

Links:

OMIM: 613529.0004; dbSNP: rs182018947

NCBI 1000 Genomes Browser:

rs182018947

Molecular consequence:

NM_001194998.2:c.2034T>G - nonsense - [Sequence Ontology: SO:0001587]
NM_014985.4:c.2034T>G - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Seckel syndrome 5 (SCKL5)
Identifiers:: MONDO: MONDO:0013443; MedGen: C3151187; Orphanet: 808; OMIM: 613823

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000045316	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2011)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000267247	Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 18, 2016)	germline	reference population	PubMed (2) [See all records that cite these PMIDs] 21131973, 25741868
SCV004171351	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000045316

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 2011)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000267247

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 18, 2016)

germline

reference population

PubMed (2)
[See all records that cite these PMIDs]

SCV004171351

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	inherited	yes	1	not provided	not provided	not provided	not provided	clinical testing
East Asian	germline	unknown	1	not provided	not provided	not provided	not provided	reference population

Citations

PubMed

CEP152 is a genome maintenance protein disrupted in Seckel syndrome.

Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tüysüz B, Nürnberg G, Kiess W, Koegl M, Baessmann I, Buruk K, Toraman B, Kayipmaz S, Kul S, Ikbal M, Turner DJ, Taylor MS, Aerts J, Scott C, et al.

Nat Genet. 2011 Jan;43(1):23-6. doi: 10.1038/ng.725. Epub 2010 Dec 5.

PubMed [citation]

PMID:: 21131973
PMCID:: PMC3430850

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000045316.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a Seckel syndrome patient (SCKL5; 613823) of Italian origin living in Germany, Kalay et al. (2011) identified compound heterozygosity for 2 mutations in the CEP152 gene: a 2034T-G transversion resulting in a tyr678-to-ter mutation (Y678X) and a splice site mutation at intron 19 (613529.0005). The splice site mutation (2694+1G-T) led to retention of the entire intron 19 in the CEP152 mRNA (r.2694G_ins3581, Ile899LeufsX29).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center, SCV000267247.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	East Asian	1	not provided	not provided	reference population	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV000784550.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004171351.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000784550	Genomic Research Center, Shahid Beheshti University of Medical Sciences	flagged submission Reason: Outlier claim with insufficient supporting evidence Notes: None (ACMG Guidelines, 2015)	Uncertain significance (Mar 5, 2018)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000784550

Genomic Research Center, Shahid Beheshti University of Medical Sciences

flagged submission

Reason: Outlier claim with insufficient supporting evidence

Notes: None

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 5, 2018)

inherited

clinical testing

PubMed (1)
[See all records that cite this PMID]

Last Updated: Nov 10, 2024

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