NM_025114.4(CEP290):c.5668G>T (p.Gly1890Ter) AND CEP290-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 13, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003147273.4

Allele description [Variation Report for NM_025114.4(CEP290):c.5668G>T (p.Gly1890Ter)]

NM_025114.4(CEP290):c.5668G>T (p.Gly1890Ter)

Gene:

CEP290:centrosomal protein 290 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q21.32

Genomic location:

Preferred name:

NM_025114.4(CEP290):c.5668G>T (p.Gly1890Ter)

HGVS:

NC_000012.12:g.88077263C>A
NG_008417.2:g.69954G>T
NM_025114.4:c.5668G>TMANE SELECT
NP_079390.3:p.Gly1890Ter
NP_079390.3:p.Gly1890Ter
LRG_694t1:c.5668G>T
LRG_694:g.69954G>T
LRG_694p1:p.Gly1890Ter
NC_000012.11:g.88471040C>A
NG_008417.1:g.69954G>T
NM_025114.3:c.5668G>T
NM_025114.3:c.[5668G>T]
NP_079390.3:p.Gly1890*

Protein change:

G1890*; GLY1890TER

Links:

OMIM: 610142.0001; dbSNP: rs137852832

NCBI 1000 Genomes Browser:

rs137852832

Molecular consequence:

NM_025114.4:c.5668G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: CEP290-related disorder
Synonyms:: CEP290-Related Disorders; CEP290-related condition
Identifiers:: MedGen: CN239314

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003836349	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 13, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004113819	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Pathogenic (Feb 26, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003836349

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 13, 2022)

unknown

clinical testing

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

SCV004113819

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Pathogenic
(Feb 26, 2024)

germline

clinical testing

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	unknown	unknown	not provided	not provided	not provided	not provided	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

Details of each submission

From Baylor Genetics, SCV003836349.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV004113819.3

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

Description

The CEP290 c.5668G>T variant is predicted to result in premature protein termination (p.Gly1890*). This variant is one of the most common pathogenic variants detected in CEP290 and has been documented as causative for Joubert syndrome (Sayer et al. 2006. PubMed ID: 16682973; Valente et al. 2006. PubMed ID: 16682970; Brancati et al. 2007. PubMed ID: 17564967; Bachmann-Gagescu et al. 2015. PubMed ID: 26092869). Different chain-terminating variants in CEP290 have been reported in patients with Meckel-Gruber syndrome (Baala et al. 2007. PubMed ID: 17564974; Frank et al. 2008. PubMed ID: 17705300) and Bardet-Biedl syndrome (Leitch et al. 2008. PubMed ID: 18327255). This variant is reported in 0.020% of alleles in individuals of South Asian descent in gnomAD. Nonsense variants in CEP290 are expected to be pathogenic, and this variant has been classified as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1333/). Given all the evidence, we interpret c.5668G>T (p.Gly1890*) 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: Oct 26, 2024

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