Submissions for variant NM_000169.3(GLA):c.640-16A>G

gnomAD frequency: 0.12447  dbSNP: rs2071397

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078287	SCV000110127	benign	not specified	2018-04-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078287	SCV000302836	benign	not specified		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000078287	SCV001442694	benign	not specified	2020-10-16	criteria provided, single submitter	clinical testing	Variant summary: GLA c.640-16A>G alters a 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 0.14 in 183214 control chromosomes in the gnomAD database, including 1381 homozygotes. The observed variant frequency is approximately 19.98 fold of the estimated maximal expected allele frequency for a pathogenic variant in GLA causing Cardiomyopathy phenotype (0.0071), strongly suggesting that the variant is benign. 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. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001521657	SCV001731036	benign	Fabry disease	2025-02-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000675280	SCV001902077	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001521657	SCV002054329	benign	Fabry disease	2021-07-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000675280	SCV005276319	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000675280	SCV000800937	benign	not provided	2015-12-15	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078287	SCV001957985	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000078287	SCV001968735	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000078287	SCV001978420	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000078287	SCV001978970	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV003114242	SCV003800593	benign	Hypertrophic cardiomyopathy	2022-09-29	no assertion criteria provided	clinical testing