ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.466-2A>G

dbSNP: rs1057517044
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409478 SCV000486659 likely pathogenic Metachromatic leukodystrophy 2016-07-14 criteria provided, single submitter clinical testing
Invitae RCV000409478 SCV003205292 likely pathogenic Metachromatic leukodystrophy 2023-02-14 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the ARSA 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 ARSA are known to be pathogenic (PMID: 8962139, 10477432). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ARSA-related conditions. ClinVar contains an entry for this variant (Variation ID: 371149). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000409478 SCV004100647 likely pathogenic Metachromatic leukodystrophy criteria provided, single submitter clinical testing The splice acceptor variant c.466-2A>G in ARSA (NM_000487.6) has been submitted to ClinVar as Likely Pathogenic, howevere no details are available for independent assesment. The variant has not been reported in affected patients.The c.466-2A>G variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant mutates a splice-acceptor sequence, potentially resulting in exon skipping and the production of abnormal proteins. For these reasons, this variant has been classified as Likely Pathogenic.

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