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NM_025114.4(CEP290):c.5587-1G>C AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 6, 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:
RCV001244155.8

Allele description [Variation Report for NM_025114.4(CEP290):c.5587-1G>C]

NM_025114.4(CEP290):c.5587-1G>C

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.5587-1G>C
HGVS:
  • NC_000012.12:g.88077345C>G
  • NG_008417.2:g.69872G>C
  • NM_025114.4:c.5587-1G>CMANE SELECT
  • LRG_694t1:c.5587-1G>C
  • LRG_694:g.69872G>C
  • NC_000012.11:g.88471122C>G
  • NM_025114.3:c.5587-1G>C
Links:
dbSNP: rs968692633
NCBI 1000 Genomes Browser:
rs968692633
Molecular consequence:
  • NM_025114.4:c.5587-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001417357Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 6, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

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 (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001417357.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 636006). This sequence change affects an acceptor splice site in intron 40 of the CEP290 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). This variant is present in population databases (no rsID available, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with Joubert syndrome, Leber congenital amaurosis, or retinitis pigmentosa (PMID: 17345604, 28559085, 29178642).

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

Last Updated: Oct 13, 2024