Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002637386 | SCV003513317 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2024-09-19 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 of the GALC gene. It does not directly change the encoded amino acid sequence of the GALC protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs755870379, gnomAD 0.01%). This variant has been observed in individual(s) with Krabbe disease (internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2194917). 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. For these reasons, this variant has been classified as Pathogenic. |