Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001031123 | SCV001194429 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2022-11-01 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 11-17 of the GALC gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. A similar copy number variant has been observed in individual(s) with Krabbe disease. This particular variant is consistent with the well known 30kb deletion, which is the most common cause of Krabbe disease in the European population, found in more than 30% of affected individuals investigated and at a frequency of 0.2% in a sample of 2,330 control European individuals. This variant has been associated with an increased risk for primary open-angle glaucoma, but the clinical relevance of this finding is unclear (PMID: 7581365, 22073273, 26795590). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that a similar copy number variant affects GALC function (PMID: 7581365). For these reasons, this variant has been classified as Pathogenic. |