Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000438611 | SCV000511910 | pathogenic | not provided | 2015-09-28 | criteria provided, single submitter | clinical testing | The c.5898+1 G>A splice site variant has been reported previously in association with Stargardt disease (Yatsenko et al., 2001; Alapati et al., 2014). This variant is expected to destroy the canonical splice donor site in intron 42, and is expected to cause abnormal gene splicing. The c.5898+1 G>A variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. |
Blueprint Genetics | RCV001075185 | SCV001240797 | pathogenic | Retinal dystrophy | 2018-11-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000438611 | SCV001404599 | pathogenic | not provided | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 42 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 individual(s) with Stargardt disease (PMID: 11379881, 27030965). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS42+1 G>A. ClinVar contains an entry for this variant (Variation ID: 377408). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Broad Institute Rare Disease Group, |
RCV001723980 | SCV001950197 | pathogenic | Retinitis pigmentosa | 2021-04-01 | criteria provided, single submitter | curation | The c.5898+1G>A variant in ABCA4 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab. |