Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670467 | SCV000795321 | likely pathogenic | Galactosylceramide beta-galactosidase deficiency | 2017-11-03 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000670467 | SCV003442792 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2023-07-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GALC protein in which other variant(s) (p.Val681Met) have been determined to be pathogenic (PMID: 23462331, 31885218). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 554777). This variant is also known as 1852delT (Leu618X). This premature translational stop signal has been observed in individual(s) with GALC-related conditions (PMID: 9338580, 29951496). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu634*) in the GALC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the GALC protein. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000670467 | SCV003844847 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2023-02-03 | criteria provided, single submitter | clinical testing | Variant summary: GALC c.1901delT (p.Leu634X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory and reported in HGMD in association with Krabbe disease. The variant was absent in 248794 control chromosomes. c.1901delT has been reported in the literature in individuals affected with Krabbe Disease (eg. Wegner_1997, Tappino_2010, Zhang_2021, Guenzel_2020, etc). These data indicate that the variant is likely to be associated with disease. GALC activity measured in COS1 cells was reported as less than 10% of wild-type (Saavedra-Martiz_2016). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000670467 | SCV000044883 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2010-12-01 | no assertion criteria provided | literature only |