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

Total submissions: 3

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