Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001382670 | SCV001581565 | pathogenic | LAMA2-related muscular dystrophy | 2020-09-15 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with congenital muscular dystrophy (PMID: 24611677, 18700894). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 49 of the LAMA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. 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. For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LAMA2 are known to be pathogenic (PMID: 18700894). |