NM_025114.4(CEP290):c.1219_1220del (p.Met407fs) AND CEP290-Related Disorders

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 20, 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:: RCV002271393.3

Allele description [Variation Report for NM_025114.4(CEP290):c.1219_1220del (p.Met407fs)]

NM_025114.4(CEP290):c.1219_1220del (p.Met407fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

12q21.32

Genomic location:

Preferred name:

NM_025114.4(CEP290):c.1219_1220del (p.Met407fs)

HGVS:

NC_000012.12:g.88121136AT[1]
NG_008417.2:g.26078AT[1]
NM_025114.4:c.1219_1220delMANE SELECT
NP_079390.3:p.Met407fs
LRG_694t1:c.1219_1220del
LRG_694:g.26078AT[1]
LRG_694p1:p.Met407fs
NC_000012.11:g.88514913AT[1]
NC_000012.11:g.88514913_88514914del
NG_008417.1:g.26078AT[1]
NM_025114.3:c.1219_1220delAT
NM_025114.4:c.1219_1220del

Protein change:

M407fs

Links:

dbSNP: rs386834148

NCBI 1000 Genomes Browser:

rs386834148

Molecular consequence:

NM_025114.4:c.1219_1220del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: CEP290-Related Disorders
Identifiers:: MedGen: CN239314

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002556025	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jun 20, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17345604, 23847139, 26626312, 19466712, 17564974 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002556025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jun 20, 2022)

germline

clinical testing

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

Citation Link

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

Citations

PubMed

Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype.

Perrault I, Delphin N, Hanein S, Gerber S, Dufier JL, Roche O, Defoort-Dhellemmes S, Dollfus H, Fazzi E, Munnich A, Kaplan J, Rozet JM.

Hum Mutat. 2007 Apr;28(4):416.

PubMed [citation]

PMID:: 17345604

Comprehensive molecular diagnosis of 179 Leber congenital amaurosis and juvenile retinitis pigmentosa patients by targeted next generation sequencing.

Wang X, Wang H, Sun V, Tuan HF, Keser V, Wang K, Ren H, Lopez I, Zaneveld JE, Siddiqui S, Bowles S, Khan A, Salvo J, Jacobson SG, Iannaccone A, Wang F, Birch D, Heckenlively JR, Fishman GA, Traboulsi EI, Li Y, Wheaton D, et al.

J Med Genet. 2013 Oct;50(10):674-88. doi: 10.1136/jmedgenet-2013-101558. Epub 2013 Jul 11.

PubMed [citation]

PMID:: 23847139
PMCID:: PMC3932025

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002556025.1

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

Description

Variant summary: CEP290 c.1219_1220delAT (p.Met407GlufsX14) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1666dupA, p.Ile556AsnfsX20; c.2722C>T, p.Arg908X; c.5182G>T, p.Glu1728X). The variant allele was found at a frequency of 7.2e-05 in 248424 control chromosomes (gnomAD). c.1219_1220delAT has been reported in the literature in multiple individuals affected with CEP290-Related Disorders including Meckel Syndrome and Leber Congenital Amaurosis (e.g. Baala_2007, Perrault_2007, Tallila_2009, Wang_2013, Astuti_2016). These data indicate that the variant is very likely to be associated with disease. Seven assessments for this variant have been submitted to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was 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 7, 2024

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