ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.121-2A>G

dbSNP: rs1567538216
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000693803 SCV000821686 pathogenic Mucopolysaccharidosis, MPS-IV-A 2023-01-28 criteria provided, single submitter clinical testing Disruption of this splice site has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 7987329). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 572428). Studies have shown that disruption of this splice site results in skipping of exon 2 and introduces a premature termination codon (PMID: 7987329). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 1 of the GALNS gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000693803 SCV001547592 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter curation Splicing variant in canonical site (PVS1_very strong); in vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; PS3_supporting); absent from gnomAD v2.1.1 (PM2_moderate)
Genome-Nilou Lab RCV000693803 SCV002045041 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-11-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000693803 SCV005641507 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2024-05-26 criteria provided, single submitter clinical testing

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