NM_025114.4(CEP290):c.4393C>T (p.Arg1465Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 23, 2023
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:: RCV000816913.7

Allele description [Variation Report for NM_025114.4(CEP290):c.4393C>T (p.Arg1465Ter)]

NM_025114.4(CEP290):c.4393C>T (p.Arg1465Ter)

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.4393C>T (p.Arg1465Ter)

Other names:

p.Arg1465Ter

HGVS:

NC_000012.12:g.88086083G>A
NG_008417.2:g.61134C>T
NM_025114.4:c.4393C>TMANE SELECT
NP_079390.3:p.Arg1465Ter
NP_079390.3:p.Arg1465Ter
LRG_694t1:c.4393C>T
LRG_694:g.61134C>T
LRG_694p1:p.Arg1465Ter
NC_000012.11:g.88479860G>A
NG_008417.1:g.61134C>T
NM_025114.3:c.4393C>T

Protein change:

R1465*

Links:

dbSNP: rs539400286

NCBI 1000 Genomes Browser:

rs539400286

Molecular consequence:

NM_025114.4:c.4393C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Familial aplasia of the vermis
Synonyms:: CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300

Name:: Meckel-Gruber syndrome
Synonyms:: DYSENCEPHALIA SPLANCHNOCYSTICA; Gruber syndrome; Dysencephalia splachnocystica
Identifiers:: MONDO: MONDO:0018921; MedGen: C0265215; OMIM: PS249000

Name:: Nephronophthisis
Synonyms:: juvenile nephronophthisis
Identifiers:: MONDO: MONDO:0019005; MedGen: C0687120; OMIM: PS256100; Human Phenotype Ontology: HP:0000090

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000957442	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 23, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16909394, 17345604, 20690115, 20683928, 29398085, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000957442

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 23, 2023)

germline

clinical testing

PubMed (6)
[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

Citations

PubMed

Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis.

den Hollander AI, Koenekoop RK, Yzer S, Lopez I, Arends ML, Voesenek KE, Zonneveld MN, Strom TM, Meitinger T, Brunner HG, Hoyng CB, van den Born LI, Rohrschneider K, Cremers FP.

Am J Hum Genet. 2006 Sep;79(3):556-61. Epub 2006 Jul 11.

PubMed [citation]

PMID:: 16909394
PMCID:: PMC1559533

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

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000957442.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Arg1465*) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). This variant is present in population databases (rs539400286, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis (PMID: 20683928, 29398085). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217626). 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: Aug 4, 2024

ClinVar

Relating variation to medicine