ClinVar Genomic variation as it relates to human health

A heterozygous deletion of exons 1-13 in PRPF31 (NM_015629.4) was identified by exome sequencing in one individual with retinitis pigmentosa ([GRCh 38] chr19:54114345_54129468x1)(PMID: 34906470). The presence of this deletion was validated by ddPCR. These breakpoints have been estimated by exome sequencing only and therefore may not reflect the true breakpoint. Inheritance information is unavailable. The patient phenotypes are nonspecific, but are consistent with cases described in the literature and/or published databases with overlapping variants. There is partial overlap with the 5’ end of the PRPF31 gene including coding sequence (NMD is expected to occur). This alteration is then predicted to lead to a truncated or absent protein. Although the PRPF31 gene has not yet been evaluated by the ClinGen dosage sensitivity working group, the full gene deletion of PRPF31 has been curated as pathogenic by the Broad Institute Rare Disease Group (Broad Institute) due to a sufficient number LoF variants in this gene being identified individuals and/or families with retinitis pigmentosa (PMID: 29260190, 29957067, 22334370, 30543658), and therefore heterozygous loss of function of the PRPF31 gene is strongly associated to PRPF31-related retinopathy. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant retinitis pigmentosa. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 0.90 points, 3: 0 points, 4-5: 0.10 points; Total: 1.0 points; Riggs 2020 (PMID: 31690835).