The c.5857+2T>C variant in USH2A has been identified in at least 3 probands with Usher syndrome, including two who were compound heterozygous for a second pathogenic variant though phase was not confirmed (PM3, PP4; PMID 20507924, 20507924, 18641288, LMM unpublished data SCV000065566.6). The allele frequency of this variant is 0.01% (2/15422) of European chromosomes by gnomAD, which is a low enough frequency to apply PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2_Supporting). This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing, though the exact impact is unknown. Exon 29 is in-frame, and if the variant results in exon skipping, it would remove <10% of the USH2A protein. However, two truncating pathogenic / likely pathogenic variants in this exon have been reported in ClinVar, which may suggest it is required for normal protein function (PVS1_Moderate). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied as specified by the Hearing Loss Expert Panel (PVS1_Moderate, PM3, PP4, PM2_Supporting).