Submissions for variant NM_016203.4(PRKAG2):c.466+2T>G

gnomAD frequency: 0.00001  dbSNP: rs962806505

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001523849	SCV001733548	uncertain significance	Cardiomyopathy	2024-03-03	criteria provided, single submitter	clinical testing	This variant causes a T to G nucleotide substitution at the +2 position of intron 3 of the PRKAG2 gene. Splice prediction tools suggest that this variant may disrupt RNA splicing. To our knowledge, RNA studies have not been reported for this variant. This variant has not been reported in individuals affected with PRKAG2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Clinical relevance of loss-of-function truncation and splice variants in the PRKAG2 gene is not clearly established. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001872008	SCV002278937	uncertain significance	Lethal congenital glycogen storage disease of heart	2024-11-06	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 3 of the PRKAG2 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), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in PRKAG2 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1170966). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
AiLife Diagnostics, AiLife Diagnostics	RCV002224083	SCV002503152	uncertain significance	not provided	2021-12-16	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004007235	SCV004839586	uncertain significance	Hypertrophic cardiomyopathy	2023-12-01	criteria provided, single submitter	clinical testing