U.S. flag

An official website of the United States government

NM_025114.4(CEP290):c.7282_7283dup (p.Tyr2429fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 12, 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:
RCV001389629.7

Allele description [Variation Report for NM_025114.4(CEP290):c.7282_7283dup (p.Tyr2429fs)]

NM_025114.4(CEP290):c.7282_7283dup (p.Tyr2429fs)

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.7282_7283dup (p.Tyr2429fs)
HGVS:
  • NC_000012.12:g.88049341_88049342dup
  • NG_008417.2:g.97875_97876dup
  • NM_001009894.3:c.*919_*920dupMANE SELECT
  • NM_025114.4:c.7282_7283dupMANE SELECT
  • NP_079390.3:p.Tyr2429fs
  • LRG_694t1:c.7282_7283dup
  • LRG_694:g.97875_97876dup
  • LRG_694p1:p.Tyr2429fs
  • NC_000012.11:g.88443117_88443118insTT
  • NC_000012.11:g.88443118_88443119dup
  • NM_025114.3:c.7282_7283dupAA
  • NM_025114.4:c.7282_7283dupAAMANE SELECT
Protein change:
Y2429fs
Links:
dbSNP: rs767231715
NCBI 1000 Genomes Browser:
rs767231715
Molecular consequence:
  • NM_001009894.3:c.*919_*920dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_025114.4:c.7282_7283dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001591055Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 12, 2023) 		germlineclinical testing

PubMed (2)
[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

Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290.

Valkenburg D, van Cauwenbergh C, Lorenz B, van Genderen MM, Bertelsen M, Pott JR, Coppieters F, de Zaeytijd J, Thiadens AAHJ, Klaver CCW, Kroes HY, van Schooneveld MJ, Preising M, Hoyng CB, Leroy BP, van den Born LI, Collin RWJ.

Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4384-4391. doi: 10.1167/iovs.18-24817.

PubMed [citation]
PMID:
30193310

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591055.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant has not been reported in the literature in individuals affected with CEP290-related conditions. This variant is present in population databases (rs767231715, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Tyr2429Serfs*8) in the CEP290 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the CEP290 protein. ClinVar contains an entry for this variant (Variation ID: 1075924). 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.Thr2457Alafs*27) have been determined to be pathogenic (PMID: 30193310). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing.

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

Last Updated: Oct 8, 2024