ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1115+5G>C

dbSNP: rs886039597
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
GeneDx RCV000255970 SCV000322497 likely pathogenic not provided 2015-12-18 criteria provided, single submitter clinical testing The c.1115+5 G>C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.1115+5 G>C variant damages or destroys the natural splice donor site of intron 8 and 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. Other splice site variants have been reported in the CAPN3 gene in association with LGMD2A (Stenson et al., 2014).
Invitae RCV000822784 SCV000963601 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2020-01-11 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. This variant has not been reported in the literature in individuals with CAPN3-related disease. ClinVar contains an entry for this variant (Variation ID: 265521). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 8 of the CAPN3 gene. It does not directly change the encoded amino acid sequence of the CAPN3 protein, but it affects a nucleotide within the consensus splice site of the intron.

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.