ClinVar Miner

Submissions for variant NM_004006.3(DMD):c.2168+1G>A

dbSNP: rs1057518207
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
GeneDx RCV000414740 SCV000491654 pathogenic not provided 2022-11-01 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32194622, 34629887, 34327855)
Labcorp Genetics (formerly Invitae), Labcorp RCV000541101 SCV000625862 pathogenic Duchenne muscular dystrophy 2023-05-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as 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: 373091). Disruption of this splice site has been observed in individuals with Duchenne muscular dystrophy (PMID: 21520333, 32194622; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 17 of the DMD 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 DMD are known to be pathogenic (PMID: 16770791, 25007885).
Neuberg Centre For Genomic Medicine, NCGM RCV000541101 SCV005042772 pathogenic Duchenne muscular dystrophy criteria provided, single submitter clinical testing The splice donor variant c.2168+1G>A in DMD gene has been reported in homozygous state in individuals with Muscular dystrophy Neri M, et al., 2020,Triana-Fonseca P, et al., 2021. The variant is novel not in any individuals in gnomAD Exomes and in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The variant affects the GT donor splice site downstream of exon 17. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing Santos R, et al., 2014. For these reasons, this variant has been classified as 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.