Submissions for variant NM_000169.3(GLA):c.1000-22C>T

gnomAD frequency: 0.33579  dbSNP: rs2071228

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000250822	SCV000302833	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000250822	SCV000330963	benign	not specified	2015-07-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000250822	SCV001442692	benign	not specified	2020-10-16	criteria provided, single submitter	clinical testing	Variant summary: GLA c.1000-22C>T is located at a position not widely known to affect splicing. The variant allele was found at a frequency of 0.24 in 181209 control chromosomes in the gnomAD database, including 5568 homozygotes. The observed variant frequency is approximately 48.21 fold of the estimated maximal expected allele frequency for a pathogenic variant in GLA causing Fabry Disease phenotype (0.005), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1000-22C>T in individuals affected with Fabry Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV000675279	SCV001887932	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001807141	SCV002054327	benign	Fabry disease	2021-07-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000675279	SCV005276318	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000675279	SCV000800935	benign	not provided	2015-10-23	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000250822	SCV001955237	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000250822	SCV001973561	benign	not specified		no assertion criteria provided	clinical testing