ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.11+5G>A (rs61751276)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000085149 SCV000336650 pathogenic not provided 2015-10-29 criteria provided, single submitter clinical testing
Invitae RCV000524808 SCV000644178 pathogenic Leber congenital amaurosis 2; Retinitis pigmentosa 20 2017-05-03 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the RPE65 gene. It does not directly change the encoded amino acid sequence of the RPE65 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs61751276, ExAC 0.02%). This variant has been observed to be homozygous or on the opposite chromosome (in trans) from several different pathogenic variants in individuals affected with retinitis pigmentosa or Leber congenital amaurosis (PMID: 9326941, 19854499, 25257057, 11462243, 20683928). It has also been shown to segregate with disease in several families (PMID: 11786058, 21211845). This variant is also known as 65+5G>A and IVS1+5G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 98825). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a variant in the consensus splice site that has been reported in many affected individuals. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000678614 SCV000044040 pathogenic Retinitis pigmentosa 20 2002-01-01 no assertion criteria provided literature only
OMIM RCV000022752 SCV000044041 pathogenic Leber congenital amaurosis 2 2002-01-01 no assertion criteria provided literature only
Retina International RCV000085149 SCV000117286 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000505050 SCV000598728 likely pathogenic Retinal dystrophy 2015-01-01 no assertion criteria provided research
Human Genetics - Radboudumc,Radboudumc RCV000678614 SCV000804701 likely pathogenic Retinitis pigmentosa 20 2016-09-01 no assertion criteria provided clinical testing

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