ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: 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 Severe early-childhood-onset retinal dystrophy 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 Center for Human Genetics 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 Severe early-childhood-onset retinal dystrophy 2021-01-30 criteria provided, single submitter clinical testing
Invitae RCV000085691 SCV001589646 pathogenic not provided 2023-11-27 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. Variants that disrupt the donor or acceptor splice site 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Stargardt disease (PMID: 19074458, 28947085, 29925512). This variant is also known as IVS35+2 T>C. ClinVar contains an entry for this variant (Variation ID: 99338). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 28118664). 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 Severe early-childhood-onset retinal dystrophy 2015-01-01 no assertion criteria provided research

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