ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.628A>T (p.Arg210Ter) (rs202131052)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000514309 SCV000484485 pathogenic not provided 2015-12-15 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514309 SCV000610755 pathogenic not provided 2017-09-06 criteria provided, single submitter clinical testing
GeneDx RCV000514309 SCV000617680 pathogenic not provided 2018-06-08 criteria provided, single submitter clinical testing The R210X variant has been reported, using alternate nomenclature, in a patient with late infantile onset Krabbe disease who also harbored a pathogenic missense variant in the GALC gene (Duffner et al. 2012). The R210X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R210X variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret this variant as pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000408648 SCV000695678 pathogenic Galactosylceramide beta-galactosidase deficiency 2016-12-08 criteria provided, single submitter clinical testing Variant summary: The GALC c.628A>T (p.Arg210X) variant results in a premature termination codon, predicted to cause a truncated or absent GALC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/115338 (1/57669), which does not exceed the estimated maximal expected allele frequency for a pathogenic GALC variant of 1/447. The variant of interest has been reported in an affected individual with late infantile Krabbe Disease, who was a compound heterozygote for the variant of interest. A clinical diagnostic laboratory cites the variant as "pathogenic." Therefore, the variant of interest has been classified as "pathogenic."
Invitae RCV000408648 SCV000820593 pathogenic Galactosylceramide beta-galactosidase deficiency 2019-02-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg210*) in the GALC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs202131052, ExAC 0.003%). This variant has been observed in an individual with low galactocerebrosidase activity, findings that are highly specific for Krabbe disease (Pubmed: 22520351, Invitae). ClinVar contains an entry for this variant (Variation ID: 369724). This variant is also known as c.580A>T, p.Arg194* in the literature. Loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000408648 SCV001132199 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2014-01-10 no assertion criteria provided clinical testing

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