Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000513102 | SCV000608710 | uncertain significance | not provided | 2017-02-01 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000513102 | SCV000701445 | pathogenic | not provided | 2016-08-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001044546 | SCV001208350 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2023-03-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 444335). This variant is also known as c.1110_1113+6del and c.1158del10. This variant has been observed in individual(s) with Krabbe disease (PMID: 21824559, 30777126). This variant is present in population databases (rs759068540, gnomAD 0.0009%). This variant results in the deletion of part of exon 10 of the GALC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001044546 | SCV001339011 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2020-03-02 | criteria provided, single submitter | clinical testing | Variant summary: GALC c.1158_1161+6del10 is located in the end of exon 10 including a canonical splice-site at intron 10 and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. 4/4 computational tools predict a significant impact on normal splicing and predict the variant abolishes a canonical 5 splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 248926 control chromosomes (gnomAD). c.1158_1161+6del10 has been reported in the literature in individuals affected with Krabbe Disease (Duffner_2011, Beltran-Quintero_2019). These data indicate that the variant may be associated with disease. At least one in vitro study reports this variant effect results in decreasing normal GALC activity. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance and pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Revvity Omics, |
RCV000513102 | SCV002024144 | pathogenic | not provided | 2022-09-21 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001044546 | SCV002093632 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2021-01-20 | no assertion criteria provided | clinical testing |