Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000673103 | SCV000798271 | likely pathogenic | Muscle eye brain disease | 2018-03-02 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002531334 | SCV003325252 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 | 2023-03-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a new termination codon (PMID: 22554691, 28424332). However the mRNA is not expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 557018). Disruption of this splice site has been observed in individual(s) with muscular dystrophy-dystroglycanopathy and/or retinitis pigmentosa (PMID: 22323514, 22554691, 26908613, 28424332). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 21 of the POMGNT1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. |