Submissions for variant NM_000292.3(PHKA2):c.918+1G>A

dbSNP: rs1601760689

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003442124	SCV004169595	likely pathogenic	not provided	2023-05-16	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32244026)
Invitae	RCV000856685	SCV004642169	pathogenic	Glycogen storage disease IXa1	2023-03-08	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 694638). Disruption of this splice site has been observed in individuals with clinical features of PHKA2-related conditions (PMID: 32244026; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the PHKA2 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 PHKA2 are known to be pathogenic (PMID: 7711737, 10330341). For these reasons, this variant has been classified as Pathogenic.
Molecular Diagnostics Laboratory, Seoul National University Hospital	RCV000856685	SCV000999210	pathogenic	Glycogen storage disease IXa1	2019-11-11	no assertion criteria provided	clinical testing
QSNICH Molecular Lab, Queen Sirikit National Institute of Child Health	RCV003127491	SCV002559896	likely pathogenic	Increased hepatic glycogen content	2022-07-01	no assertion criteria provided	clinical testing