ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.850G>A (p.Gly284Ser)

gnomAD frequency: 0.00003  dbSNP: rs377274761
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000415223 SCV000492714 likely pathogenic Leukodystrophy; Status epilepticus; Global developmental delay; Seizure; Fetal growth restriction; EEG abnormality; Nystagmus; Hemiparesis; Strabismus; Progressive visual loss; Amblyopia; Small for gestational age; Breech presentation; Neonatal hypoglycemia; Developmental regression; Loss of ambulation; EMG abnormality; EMG: axonal abnormality; Dysmyelinating leukodystrophy 2015-10-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588587 SCV000695673 pathogenic Galactosylceramide beta-galactosidase deficiency 2016-11-08 criteria provided, single submitter clinical testing Variant summary: The GALC c.850G>A (p.Gly284Ser) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 1/120666 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic GALC variant (0.0022361). This variant has been reported in multiple affected individuals with evidence of co-segregation. Functional assay showed variant with 5% of WT activity (De Gasperi et al 1996). Taken together, this variant is classified as pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000588587 SCV001369176 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic.
Invitae RCV000588587 SCV001416954 pathogenic Galactosylceramide beta-galactosidase deficiency 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 284 of the GALC protein (p.Gly284Ser). This variant is present in population databases (rs377274761, gnomAD 0.002%). This missense change has been observed in individual(s) with Krabbe disease or its clinical features (PMID: 8940268, 22520351, 29286531). It has also been observed to segregate with disease in related individuals. This variant is also known as p.G268S. ClinVar contains an entry for this variant (Variation ID: 374024). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALC protein function. Experimental studies have shown that this missense change affects GALC function (PMID: 8940268, 27638593). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001785610 SCV002021209 pathogenic not provided 2021-04-14 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000588587 SCV002581113 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2022-07-27 criteria provided, single submitter clinical testing
Counsyl RCV000588587 SCV000791856 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2017-05-25 no assertion criteria provided clinical testing

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