Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001046029 | SCV001209911 | likely pathogenic | Charcot-Marie-Tooth disease type 4 | 2022-06-09 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: 843411). Disruption of this splice site has been observed in individual(s) with Charcot-Marie-Tooth disease (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 5 of the PRX 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 PRX are known to be pathogenic (PMID: 11133365). |
Ambry Genetics | RCV003363067 | SCV004072586 | likely pathogenic | Inborn genetic diseases | 2023-06-26 | criteria provided, single submitter | clinical testing | The c.184+2T>C intronic alteration results from a T to C substitution 2 nucleotides after exon 5 (coding exon 2) of the PRX gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was detected in the homozygous state in an individual with a clinical diagnosis of Charcot-Marie-Tooth disease (external communication). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on the available evidence, this alteration is classified as likely pathogenic. |