ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.5018+2T>C (rs61750562)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408523 SCV000281910 pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000085691 SCV000511904 pathogenic not provided 2018-06-22 criteria provided, single submitter clinical testing The c.5018+2 T>C variant has been published as a pathogenic variant in association with Stargardt disease (Cideciyan et al., 2009; Rivera et al., 2000; Allikmets et al., 1997). The c.5018+2 T>C splice site variant is expected to destroy the canonical splice donor site in intron 35, and to cause abnormal gene splicing. This is expected to lead to either an abnormal message which is subject to nonsense mediated mRNA decay or to an abnormal protein product if the message is used for protein translation. The c.5018+2 T>C variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000085691 SCV000574764 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001074630 SCV001240222 pathogenic Retinal dystrophy 2019-02-05 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000085691 SCV001447612 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute of Medical Molecular Genetics, University of Zurich RCV000408523 SCV001548059 likely pathogenic Stargardt disease 1 2021-01-30 criteria provided, single submitter clinical testing
Invitae RCV000085691 SCV001589646 pathogenic not provided 2020-10-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 35 of the ABCA4 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Stargardt disease (PMID: 19074458, 29925512, 28947085). This variant is also known as IVS35+2 T>C in the literature. ClinVar contains an entry for this variant (Variation ID: 99338). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 28118664). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). For these reasons, this variant has been classified as Pathogenic.
Retina International RCV000085691 SCV000117831 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000408523 SCV000598988 likely pathogenic Stargardt disease 1 2015-01-01 no assertion criteria provided research

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