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NM_025114.4(CEP290):c.7328_7332dup (p.Val2445fs) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 20, 2024
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:
RCV004029060.1

Allele description [Variation Report for NM_025114.4(CEP290):c.7328_7332dup (p.Val2445fs)]

NM_025114.4(CEP290):c.7328_7332dup (p.Val2445fs)

Genes:
RLIG1:RNA 5'-phosphate and 3'-OH ligase 1 [Gene - HGNC]
CEP290:centrosomal protein 290 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
12q21.32
Genomic location:
Preferred name:
NM_025114.4(CEP290):c.7328_7332dup (p.Val2445fs)
HGVS:
  • NC_000012.12:g.88049292CTTCT[3]
  • NG_008417.2:g.97916AGAAG[3]
  • NM_001009894.3:c.*870CTTCT[3]MANE SELECT
  • NM_025114.4:c.7328_7332dupMANE SELECT
  • NP_079390.3:p.Val2445fs
  • LRG_694t1:c.7328_7332dup
  • LRG_694:g.97916AGAAG[3]
  • LRG_694p1:p.Val2445fs
  • NC_000012.11:g.88443068_88443069insCTTCT
  • NC_000012.11:g.88443069CTTCT[3]
  • NM_025114.3:c.7328_7332dup
  • NM_025114.3:c.7328_7332dupAGAAG
Protein change:
V2445fs
Links:
dbSNP: rs747138345
NCBI 1000 Genomes Browser:
rs747138345
Molecular consequence:
  • NM_001009894.3:c.*870CTTCT[3] - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_025114.4:c.7328_7332dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004926252Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Feb 20, 2024) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Molecular genetics of Leber congenital amaurosis in Chinese: New data from 66 probands and mutation overview of 159 probands.

Xu Y, Xiao X, Li S, Jia X, Xin W, Wang P, Sun W, Huang L, Guo X, Zhang Q.

Exp Eye Res. 2016 Aug;149:93-99. doi: 10.1016/j.exer.2016.06.019. Epub 2016 Jun 30.

PubMed [citation]
PMID:
27375279

Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy.

Xu K, Xie Y, Sun T, Zhang X, Chen C, Li Y.

Br J Ophthalmol. 2020 Jul;104(7):932-937. doi: 10.1136/bjophthalmol-2019-314281. Epub 2019 Oct 19.

PubMed [citation]
PMID:
31630094
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV004926252.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The c.7328_7332dupAGAAG (p.V2445Rfs*3) alteration, located in exon 54 (coding exon 53) of the CEP290 gene, consists of a duplication of AGAAG at position 7328, causing a translational frameshift with a predicted alternate stop codon after 3 amino acids. This alteration occurs at the 3' terminus of the CEP290 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 1.4% of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). Based on data from gnomAD, the AGAAGAGAAG allele has an overall frequency of 0.004% (9/246068) total alleles studied. The highest observed frequency was 0.05% (9/17952) of East Asian alleles. This variant has been identified likely in trans with another CEP290 variant in multiple individuals with features consistent with CEP290-related ciliopathy (Liu, 2021; Xu, 2020; Xu, 2016). Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: Apr 7, 2025