ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.1992-2A>G

dbSNP: rs797044626
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000173621 SCV000224746 pathogenic not provided 2014-09-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000173621 SCV001472856 pathogenic not provided 2019-12-06 criteria provided, single submitter clinical testing The ABCD1 c.1992-2A>G variant (rs797044626) is reported in the literature in an individual affected with X-linked adrenoleukodystrophy (Carra-Dalliere 2013). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant abolishes the canonical splice acceptor site of intron 9, which is likely to disrupt gene function. Based on available information, this variant is considered to be pathogenic. References: Carra-Dalliere C et al. Adult-onset cerebral X-linked adrenoleukodystrophy with major contrast-enhancement mimicking acquired disease. Clin Neurol Neurosurg. 2013 Sep;115(9):1906-7.
Invitae RCV003624406 SCV004539102 uncertain significance Adrenoleukodystrophy 2022-11-24 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 193547). Disruption of this splice site has been observed in individual(s) with clinical features of ABCD1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 9 of the ABCD1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.

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