ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.245-2A>G

dbSNP: rs1352162269
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV001578543 SCV001547632 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research Splicing variant in canonical site (PVS1_strong); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_supporting); very low frequency in gnomAD v2.1.1 (PM2_moderate)
Labcorp Genetics (formerly Invitae), Labcorp RCV001578543 SCV002969456 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2022-10-30 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the GALNS 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 GALNS are known to be pathogenic (PMID: 12442278). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. 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: 1048442). Disruption of this splice site has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 34387910).
Revvity Omics, Revvity RCV001578543 SCV004238208 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2023-03-07 criteria provided, single submitter clinical testing

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