ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1814dup (p.Tyr605Ter) (rs766007316)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781391 SCV000919386 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2017-10-31 criteria provided, single submitter clinical testing Variant summary: The GALC c.1814dupA (p.Tyr605X) 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. This variant was found in 2/244526 control chromosomes (gnomAD) at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic GALC variant (0.0022361). The variant of interest has not, to our knowledge, been reported in affected individuals via publications. An internal patient with Krabbe disease diagnosed as an infant (<1 yo) carried this variant homozygously. A clinical diagnostic laboratory cites the variant with a classification of "pathogenic." Taken together, this variant is classified as likely pathogenic.
Invitae RCV000781391 SCV001382219 pathogenic Galactosylceramide beta-galactosidase deficiency 2019-09-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr605*) in the GALC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs766007316, ExAC 0.01%). This variant has been observed in an individual affected with Krabbe disease (PMID: 30777126). This variant is also known as c.1766dupA in the literature. ClinVar contains an entry for this variant (Variation ID: 633226). 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.
Human Genetics - Radboudumc,Radboudumc RCV001724154 SCV001959367 pathogenic not provided no assertion criteria provided clinical testing

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