Submissions for variant NM_000153.4(GALC):c.1921A>G (p.Thr641Ala)

gnomAD frequency: 0.95462  dbSNP: rs421262

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078197	SCV000110035	benign	not specified	2015-10-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078197	SCV000302714	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000290698	SCV000389234	benign	Galactosylceramide beta-galactosidase deficiency	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586993	SCV000695675	benign	not provided	2016-05-16	criteria provided, single submitter	clinical testing	Variant summary: The GALC c.1921A>G (p.Thr641Ala) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome (SNPs&GO not captured due to isoform mismatch). This variant was found in 118335/120404 control chromosomes (58239 homozygotes) at a frequency of 0.9828162, which is approximately 440 times the estimated maximal expected allele frequency of a pathogenic GALC variant (0.0022361), highly suggesting this variant is a benign polymorphism and the ancestral allele. The variant has been found to co-occur in Krabbe Disease patients with compound heterozygous pathogenic variants that would explain the patients phenotype. In addition, a clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as Benign.
Invitae	RCV000290698	SCV001728015	benign	Galactosylceramide beta-galactosidase deficiency	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000290698	SCV001750146	benign	Galactosylceramide beta-galactosidase deficiency	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000586993	SCV001898491	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27638593, 24078576, 27884173, 20981092, 10477434)
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000290698	SCV000733401	benign	Galactosylceramide beta-galactosidase deficiency		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000586993	SCV000800900	benign	not provided	2015-10-19	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000290698	SCV001464119	benign	Galactosylceramide beta-galactosidase deficiency	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000078197	SCV001924203	benign	not specified		no assertion criteria provided	clinical testing