U.S. flag

An official website of the United States government

NM_000329.3(RPE65):c.1451-1G>A AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 15, 2022
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:
RCV003120686.4

Allele description [Variation Report for NM_000329.3(RPE65):c.1451-1G>A]

NM_000329.3(RPE65):c.1451-1G>A

Gene:
RPE65:retinoid isomerohydrolase RPE65 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p31.3
Genomic location:
Preferred name:
NM_000329.3(RPE65):c.1451-1G>A
HGVS:
  • NC_000001.11:g.68429928C>T
  • NG_008472.2:g.25032G>A
  • NM_000329.3:c.1451-1G>AMANE SELECT
  • NM_001406853.1:c.1343-1G>A
  • NM_001406856.1:c.1175-1G>A
  • NM_001406857.1:c.1175-1G>A
  • NC_000001.10:g.68895611C>T
Links:
dbSNP: rs1317871521
NCBI 1000 Genomes Browser:
rs1317871521
Molecular consequence:
  • NM_000329.3:c.1451-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406853.1:c.1343-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406856.1:c.1175-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406857.1:c.1175-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Leber congenital amaurosis 2 (LCA2)
Synonyms:
AMAUROSIS CONGENITA OF LEBER II; Amaurosis congenita of Leber, type 2; RPE65-Related Leber Congenital Amaurosis
Identifiers:
MONDO: MONDO:0008765; MedGen: C1859844; Orphanet: 65; OMIM: 204100
Name:
Retinitis pigmentosa 20 (RP20)
Synonyms:
RP 20
Identifiers:
MONDO: MONDO:0013425; MedGen: C3151086; Orphanet: 791; OMIM: 613794

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
SCV003786327Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 15, 2022) 		germlineclinical testing

PubMed (5)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003786327.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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: 1321180). Disruption of this splice site has been observed in individual(s) with autosomal recessive Leber congenital amaurosis (PMID: 31273949, 31957135). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change affects an acceptor splice site in intron 13 of the RPE65 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.

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

Last Updated: May 7, 2024