ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.195+19G>A (rs189853941)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000248468 SCV000302715 benign not specified criteria provided, single submitter clinical testing
GeneDx RCV001722287 SCV000515895 likely benign not provided 2020-11-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000248468 SCV001372311 benign not specified 2020-06-18 criteria provided, single submitter clinical testing Variant summary: GALC c.195+19G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0017 in 113460 control chromosomes, predominantly at a frequency of 0.003 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in GALC causing Krabbe Disease phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.195+19G>A in individuals affected with Krabbe Disease and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV001515699 SCV001723834 benign Galactosylceramide beta-galactosidase deficiency 2020-11-30 criteria provided, single submitter clinical testing

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