ClinVar Miner

Submissions for variant NM_001605.3(AARS1):c.2177+5G>A

dbSNP: rs2152153454
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV002227376 SCV002506285 uncertain significance not provided 2022-02-07 criteria provided, single submitter clinical testing The AARS1 c.2177+5G>A variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant in a highly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by disrupting the nearby canonical donor splice site. However, loss of function is not an established mechanism of disease for this gene, and without functional studies the effect on splicing is unknown. Due to limited information, the clinical significance of this variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV002237197 SCV002510161 uncertain significance Charcot-Marie-Tooth disease type 2 2024-02-24 criteria provided, single submitter clinical testing This sequence change falls in intron 15 of the AARS gene. It does not directly change the encoded amino acid sequence of the AARS protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1679497). 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. 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.
PreventionGenetics, part of Exact Sciences RCV003408174 SCV004109724 uncertain significance AARS1-related disorder 2023-04-20 criteria provided, single submitter clinical testing The AARS1 c.2177+5G>A variant is predicted to interfere with splicing. Specifically, this variant is predicted to strongly reduce the strength of the nearby splice donor site (Alamut Visual Plus v1.6.1). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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