ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.20787+2T>C

gnomAD frequency: 0.00001  dbSNP: rs1337287633
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673439 SCV000798641 likely pathogenic Nemaline myopathy 2 2018-03-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000673439 SCV002266037 likely pathogenic Nemaline myopathy 2 2023-01-20 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 557313). This variant has not been reported in the literature in individuals affected with NEB-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change affects a donor splice site in intron 137 of the NEB 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 NEB are known to be pathogenic (PMID: 25205138).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271561 SCV002555757 likely pathogenic Nemaline myopathy 2024-09-19 criteria provided, single submitter clinical testing Variant summary: NEB c.20787+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of NEB function. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5 splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 248568 control chromosomes. To our knowledge, no occurrence of c.20787+2T>C in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 557313). Based on the evidence outlined above, the variant was 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.