ClinVar Miner

Submissions for variant NM_001080467.3(MYO5B):c.3277-2A>G

gnomAD frequency: 0.00001  dbSNP: rs1212171741
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University RCV001250573 SCV001425433 likely pathogenic Congenital microvillous atrophy 2020-02-20 criteria provided, single submitter clinical testing MYO5B c.3277-2A>G (rs1212171741) is rare (<0.1%) in large population datasets (gnomAD: 1/31404 total alleles, MAF 0.0003%), and has not been reported in ClinVar nor the literature, to our knowledge. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing. We consider this variant to be likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001879780 SCV002147001 pathogenic not provided 2021-05-11 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 24 of the MYO5B 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 MYO5B are known to be pathogenic (PMID: 18724368, 20186687). This variant has been observed in individual(s) with clinical features of microvillus inclusion disease (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 973894). 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. For these reasons, this variant has been classified as Pathogenic.

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