ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.24219+1G>A (rs755239192)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000387492 SCV000329654 pathogenic not provided 2015-09-10 criteria provided, single submitter clinical testing The c.24219+1G>A pathogenic variant in the NEB gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 170. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.24219+1G>A variant was not observed in approximately 2300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.24219+1G>A as a pathogenic variant.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000625834 SCV000746397 pathogenic Nemaline myopathy 2 2017-12-03 criteria provided, single submitter clinical testing
Counsyl RCV000625834 SCV000790290 likely pathogenic Nemaline myopathy 2 2017-03-09 criteria provided, single submitter clinical testing
Invitae RCV000625834 SCV001209384 likely pathogenic Nemaline myopathy 2 2019-12-13 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 170 of the NEB gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs755239192, ExAC 0.01%). This variant has not been reported in the literature in individuals with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 279977). 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 NEB are known to be pathogenic (PMID: 25205138). 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.

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.