ClinVar Miner

Submissions for variant NM_016239.4(MYO15A):c.8341-2A>C

gnomAD frequency: 0.00002  dbSNP: rs778404517
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000615114 SCV000731689 pathogenic Rare genetic deafness 2017-06-13 criteria provided, single submitter clinical testing The c.8341-2A>C variant in MYO15A has not been previously reported in individual s with hearing loss, but has been identified in 4/126622 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSN P rs778404517). Although this variant has been seen in the general population, i ts frequency is low enough to be consistent with a carrier frequency for recessi ve hearing loss. This variant occurs in the invariant region (+/- 1,2) of the sp lice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. In summary, this variant meets criteria to be class ified as pathogenic for autosomal recessive hearing loss based on the predicted impact to the protein.
Labcorp Genetics (formerly Invitae), Labcorp RCV003727781 SCV004534795 likely pathogenic not provided 2023-09-09 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MYO15A-related conditions. ClinVar contains an entry for this variant (Variation ID: 517420). 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. This variant is present in population databases (rs778404517, gnomAD 0.003%). This sequence change affects an acceptor splice site in intron 46 of the MYO15A 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 MYO15A are known to be pathogenic (PMID: 17546645).

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