Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001207376 | SCV001378723 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2019-09-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GALNS are known to be pathogenic (PMID: 12442278). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individuals affected with MPS IVA (PMID: 25252036, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 10 of the GALNS gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV001207376 | SCV001547901 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | research | 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_strong); absent from gnomAD v2.1.1 (PM2_moderate) |
Genome- |
RCV001207376 | SCV002045001 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-11-07 | criteria provided, single submitter | clinical testing |