ClinVar Miner

Submissions for variant NM_005751.5(AKAP9):c.11687-2A>G

gnomAD frequency: 0.00002  dbSNP: rs1176473354
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002029786 SCV002110298 uncertain significance Long QT syndrome 2021-04-16 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with AKAP9-related conditions. 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. Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 49 of the AKAP9 gene. It does not directly change the encoded amino acid sequence of the AKAP9 protein. It affects a nucleotide within the consensus splice site of the intron.
Ambry Genetics RCV002329778 SCV002626668 uncertain significance Cardiovascular phenotype 2021-10-28 criteria provided, single submitter clinical testing The c.11687-2A>G intronic variant results from an A to G substitution two nucleotides before coding exon 50 of the AKAP9 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of AKAP9 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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