Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV003337951 | SCV004048411 | likely pathogenic | Arthrogryposis, distal, with impaired proprioception and touch | criteria provided, single submitter | clinical testing | The splice donor variant c.1527+2T>C in PIEZO2 (NM_022068.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1527+2T>C variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant mutates a splice-donor sequence, potentially resulting in the retention of large segments of intronic DNA by the mRNA and nonfunctional proteins. The c.1527+2T>C variant is a loss of function variant in the gene PIEZO2, which is intolerant of Loss of Function variants, as indicated by the presence of existing pathogenic loss of function variant. For these reasons, this variant has been classified as Likely Pathogenic. |