Submissions for variant NM_000642.3(AGL):c.294-2A>T

dbSNP: rs1057516868

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000412181	SCV001575137	likely pathogenic	Glycogen storage disease type III	2023-11-11	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 3 of the AGL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of AGL-related conditions (PMID: 31130284). ClinVar contains an entry for this variant (Variation ID: 370920). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity	RCV000412181	SCV002022997	pathogenic	Glycogen storage disease type III	2023-12-27	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000412181	SCV002060306	likely pathogenic	Glycogen storage disease type III	2021-11-19	criteria provided, single submitter	clinical testing	NM_000642.2(AGL):c.294-2A>T is a canonical splice variant classified as likely pathogenic in the context of glycogen storage disease type III. c.294-2A>T has not been observed in cases with relevant disease. Functional assessments of this variant are not available in the literature. c.294-2A>T has not been observed in population frequency databases. In summary, NM_000642.2(AGL):c.294-2A>T is a canonical splice variant in a gene where loss of function is a known mechanism of disease and is predicted to disrupt protein function. Please note: this variant was assessed in the context of healthy population screening.
CeGaT Center for Human Genetics Tuebingen	RCV002058838	SCV002496901	pathogenic	not provided	2022-03-01	criteria provided, single submitter	clinical testing	AGL: PVS1, PM2
Fulgent Genetics, Fulgent Genetics	RCV000412181	SCV002784004	likely pathogenic	Glycogen storage disease type III	2021-10-25	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000412181	SCV004049916	likely pathogenic	Glycogen storage disease type III	2023-04-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000412181	SCV004215291	likely pathogenic	Glycogen storage disease type III	2023-06-03	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000412181	SCV004804867	pathogenic	Glycogen storage disease type III	2024-03-17	criteria provided, single submitter	research
Natera, Inc.	RCV000412181	SCV002091435	likely pathogenic	Glycogen storage disease type III	2020-02-03	no assertion criteria provided	clinical testing