ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.5461-10T>C (rs1800728)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV000210325 SCV000259075 likely pathogenic Bull's eye maculopathy 2015-01-19 no assertion criteria provided clinical testing
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV000210327 SCV000259078 likely pathogenic Retinal dystrophy 2015-01-21 no assertion criteria provided clinical testing
Division of Human Genetics,Children's Hospital of Philadelphia RCV000008366 SCV000536892 pathogenic Cone-rod dystrophy 3 2016-02-23 no assertion criteria provided research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078669 SCV000229932 pathogenic not provided 2017-05-24 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763440 SCV000894207 pathogenic Cone-rod dystrophy 3; Age-related macular degeneration 2; Stargardt disease 1; Retinitis pigmentosa 19 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000078669 SCV000321356 pathogenic not provided 2018-08-11 criteria provided, single submitter clinical testing The c.5461-10 T>C variant in the ABCA4 gene has been reported previously in the homozygous state and in the presence of a second ABCA4 pathogenic variant, in association with Stargardt disease and cone-rod dystrophy (Webster et al., 2001; Klevering et al., 2005; Burke et al., 2010; Alapati et al., 2014; Sangermano et al., 2016). A minigene splice assay in HEK293T cells showed the c.5461-10 T>C variant construct had 100% exon 39 skipping, which was confirmed by cDNA sequencing (Sangermano et al., 2016). Furthermore, a study examining the RNA from the fibroblast cells from individuals harboring the c.5461-10 T>C variant identified a reduction in full-length mRNA and the presence of alternatively splice mRNAs where exons 39-40 were skipped (Aukrust et al., 2017). The c.5461-10 T>C variant is reported as likely pathogenic in ClinVar by a different clinical laboratory, but additional evidence is not available (ClinVar SCV000229932.3, Landrum et al., 2016). The c.5461-10 T>C variant is observed in 59/126,148 (0.05%) alleles from individuals of non-Finnish European background, with no homozygous individuals reported, in large population cohorts (Lek et al., 2016). This nucleotide substitution occurs at a position that is conserved in mammals. We interpret c.5461-10 T>C as a pathogenic variant.
Human Genetics - Radboudumc,Radboudumc RCV000678511 SCV000804582 pathogenic Age-related macular degeneration 2 2016-09-01 no assertion criteria provided clinical testing
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000177965 SCV000281925 pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787510 SCV000926476 pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000504857 SCV000926477 pathogenic Macular dystrophy 2018-04-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787771 SCV000926776 pathogenic Stargardt disease 2018-04-01 no assertion criteria provided research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504857 SCV000598996 likely pathogenic Macular dystrophy 2015-01-01 no assertion criteria provided research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000210327 SCV000598997 likely pathogenic Retinal dystrophy 2015-01-01 no assertion criteria provided research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000177965 SCV000598998 likely pathogenic Stargardt disease 1 2015-01-01 no assertion criteria provided research
OMIM RCV000008366 SCV000028574 pathogenic Cone-rod dystrophy 3 2008-07-01 no assertion criteria provided literature only
Retina International RCV000078669 SCV000117870 not provided not provided no assertion provided not provided

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