ClinVar Miner

Submissions for variant NM_004999.4(MYO6):c.2078-2A>G

dbSNP: rs1777874560
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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 RCV001879949 SCV002273849 likely pathogenic not provided 2021-10-28 criteria provided, single submitter clinical testing 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. 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: 978024). This variant has not been reported in the literature in individuals affected with MYO6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 20 of the MYO6 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 MYO6 are known to be pathogenic (PMID: 12687499, 18348273, 23767834, 25999546, 30582396).
Clinical Genomics Laboratory, Stanford Medicine RCV001255960 SCV001427061 likely pathogenic Autosomal dominant nonsyndromic hearing loss 22 2019-05-29 no assertion criteria provided clinical testing The c.2078-2A>G variant in the MYO6 gene has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The c.2078-2A>G variant alters the canonical acceptor splice site in intron 20, which is predicted to result in abnormal gene splicing. Heterozygous loss of function is an established mechanism of disease for the MYO6 gene. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the c.2078-2A>G variant as likely pathogenic for autosomal dominant nonsydromic sensorineural hearing loss based on the information above. [ACMG evidence codes used: PVS1_Strong; PM2]

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