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NM_025114.4(CEP290):c.7263dup (p.Glu2422Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 16, 2021
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:
RCV001884185.3

Allele description [Variation Report for NM_025114.4(CEP290):c.7263dup (p.Glu2422Ter)]

NM_025114.4(CEP290):c.7263dup (p.Glu2422Ter)

Genes:
RLIG1:RNA 5'-phosphate and 3'-OH ligase 1 [Gene - HGNC]
CEP290:centrosomal protein 290 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
12q21.32
Genomic location:
Preferred name:
NM_025114.4(CEP290):c.7263dup (p.Glu2422Ter)
HGVS:
  • NC_000012.12:g.88049366dup
  • NG_008417.2:g.97856dup
  • NM_001009894.3:c.*944dupMANE SELECT
  • NM_025114.4:c.7263dupMANE SELECT
  • NP_079390.3:p.Glu2422Ter
  • LRG_694t1:c.7263dup
  • LRG_694:g.97856dup
  • LRG_694p1:p.Glu2422Ter
  • NC_000012.11:g.88443137_88443138insA
  • NC_000012.11:g.88443143dup
  • NG_008417.1:g.97856dup
Protein change:
E2422*
Links:
dbSNP: rs1219184437
NCBI 1000 Genomes Browser:
rs1219184437
Molecular consequence:
  • NM_001009894.3:c.*944dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_025114.4:c.7263dup - 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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002153845Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 16, 2021)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4.

Sayer JA, Otto EA, O'Toole JF, Nurnberg G, Kennedy MA, Becker C, Hennies HC, Helou J, Attanasio M, Fausett BV, Utsch B, Khanna H, Liu Y, Drummond I, Kawakami I, Kusakabe T, Tsuda M, Ma L, Lee H, Larson RG, Allen SJ, Wilkinson CJ, et al.

Nat Genet. 2006 Jun;38(6):674-81. Epub 2006 May 7.

PubMed [citation]
PMID:
16682973

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
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002153845.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CEP290 protein in which other variant(s) (p.Leu2448Thrfs*8) have been determined to be pathogenic (PMID: 16682973, 16909394, 29588463; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. A different variant (c.7264G>T) giving rise to the same protein effect has been determined to be pathogenic (Invitae). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu2422*) in the CEP290 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 58 amino acid(s) of the CEP290 protein.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024