ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.62+1G>A (rs786205048)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558865 SCV000645649 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2017-08-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 1 of the MECP2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. The MECP2 gene has multiple clinically relevant isoforms. The c.62+1G>A variant occurs in alternate transcript NM_001110792.1, which corresponds to position c.-99+1G>A in NM_004992.3, the primary transcript listed in the Methods. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with Rett syndrome (PMID: 15737703). It is also known as "Ex1 donor site" in the literature. ClinVar contains an entry for this variant (Variation ID: 189776). 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MECP2 are known to be pathogenic (PMID: 12180070). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000170294 SCV001142097 pathogenic Rett syndrome 2019-05-28 criteria provided, single submitter clinical testing
RettBASE RCV000170294 SCV000222628 uncertain significance Rett syndrome 2008-02-18 no assertion criteria provided curation

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