Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| EGL Genetic Diagnostics, |
RCV000344890 | SCV000340661 | pathogenic | not provided | 2016-03-23 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000650387 | SCV000772231 | pathogenic | Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A7; Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 7 | 2017-10-23 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 8 of the ISPD gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Walker-Warburg syndrome (PMID: 22522420). ClinVar contains an entry for this variant (Variation ID: 31561). Experimental studies have shown that this splice change results in a defect in alpha dystroglycan processing, and loss of functional glycosylation and laminin binding (PMID: 22522420). 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 ISPD are known to be pathogenic (PMID: 23288328). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000024269 | SCV000045560 | pathogenic | Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A7 | 2012-05-01 | no assertion criteria provided | literature only |