ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.1051+3A>G

gnomAD frequency: 0.00002  dbSNP: rs376499470
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000819180 SCV000959826 uncertain significance Lethal congenital glycogen storage disease of heart 2023-10-24 criteria provided, single submitter clinical testing This sequence change falls in intron 9 of the PRKAG2 gene. It does not directly change the encoded amino acid sequence of the PRKAG2 protein. It affects a nucleotide within the consensus splice site. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 661703). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.
Color Diagnostics, LLC DBA Color Health RCV001183651 SCV001349445 uncertain significance Cardiomyopathy 2023-11-06 criteria provided, single submitter clinical testing This variant causes an A to G nucleotide substitution at the +3 position of intron 9 of the PRKAG2 gene. Splice site prediction tools are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional 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 been identified in 3/281202 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
GeneDx RCV001569388 SCV001793454 likely benign not provided 2020-11-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV003307544 SCV004007674 uncertain significance Cardiovascular phenotype 2023-05-13 criteria provided, single submitter clinical testing The c.1051+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 9 in the PRKAG2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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