NM_001330691.3(CEP78):c.1424del (p.Val475fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 18, 2024
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:: RCV001092272.20

Allele description

NM_001330691.3(CEP78):c.1424del (p.Val475fs)

Gene:

CEP78:centrosomal protein 78 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

9q21.2

Genomic location:

Preferred name:

NM_001330691.3(CEP78):c.1424del (p.Val475fs)

HGVS:

NC_000009.12:g.78262950del
NG_053171.1:g.31889del
NM_001098802.3:c.1427del
NM_001330691.3:c.1424delMANE SELECT
NM_001330693.3:c.1424del
NM_001330694.2:c.1424del
NM_001349838.2:c.1424del
NM_001349839.2:c.1427del
NM_001349840.2:c.1427del
NM_032171.3:c.1427del
NP_001092272.1:p.Val476fs
NP_001317620.1:p.Val475fs
NP_001317622.1:p.Val475fs
NP_001317623.1:p.Val475fs
NP_001336767.1:p.Val475fs
NP_001336768.1:p.Val476fs
NP_001336769.1:p.Val476fs
NP_115547.1:p.Val476fs
NC_000009.11:g.80877866del
NC_000009.11:g.80877866del
NM_001098802.1:c.1427del
NM_001098802.2:c.1427del

Protein change:

V475fs

Links:

dbSNP: rs1196886096

NCBI 1000 Genomes Browser:

rs1196886096

Molecular consequence:

NM_001098802.3:c.1427del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330691.3:c.1424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330693.3:c.1424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330694.2:c.1424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001349838.2:c.1424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001349839.2:c.1427del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001349840.2:c.1427del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_032171.3:c.1427del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001248693	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jul 1, 2019)	germline	clinical testing	Citation Link,
SCV001447305	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004409446	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 27588451, 27588452, 27627988, 32531858, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001248693

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Jul 1, 2019)

germline

clinical testing

Citation Link,

SCV001447305

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 23, 2020)

germline

clinical testing

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

SCV004409446

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	3	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

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

Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

Nikopoulos K, Farinelli P, Giangreco B, Tsika C, Royer-Bertrand B, Mbefo MK, Bedoni N, Kjellström U, El Zaoui I, Di Gioia SA, Balzano S, Cisarova K, Messina A, Decembrini S, Plainis S, Blazaki SV, Khan MI, Micheal S, Boldt K, Ueffing M, Moulin AP, Cremers FPM, et al.

Am J Hum Genet. 2016 Sep 1;99(3):770-776. doi: 10.1016/j.ajhg.2016.07.009.

PubMed [citation]

PMID:: 27588451
PMCID:: PMC5011074

See all PubMed Citations (6)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001248693.21

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

#	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		3	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001447305.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	germline	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV004409446.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Val476Glyfs*2) in the CEP78 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP78 are known to be pathogenic (PMID: 27588451, 27588452, 27627988). This variant is present in population databases (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with cone-rod dystrophy (PMID: 32531858). ClinVar contains an entry for this variant (Variation ID: 813161). 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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 12, 2024

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