ClinVar Miner

Submissions for variant NM_001256545.2(MEGF10):c.2857-2A>G (rs199750143)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000529609 SCV000651945 likely pathogenic Myopathy, areflexia, respiratory distress, and dysphagia, early-onset 2017-04-18 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 22 of the MEGF10 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with a MEGF10-related disease. In summary, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547), and loss-of-function variants in MEGF10 are known to be pathogenic (PMID: 22101682). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV000529609 SCV000915108 uncertain significance Myopathy, areflexia, respiratory distress, and dysphagia, early-onset 2018-10-15 criteria provided, single submitter clinical testing The MEGF10 c.2857-2A>G variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. The c.2857-2A>G variant is reported at a frequency of 0.000259 in the Latino population of the Exome Aggregation Consortium. Due to the potential impact of splice acceptor variants and the lack of clarifying evidence, the c.2857-2A>G variant is classified as a variant of unknown significance but suspicious for pathogenicity for myopathy, early-onset, areflexia, respiratory distress, and dysphagia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.