Using PMS2 and PMS2CL as an example: For both gene and pseudogene, exons 11-15 are very similar and the SOPHiA DDM™ Platform provides a warning for all variants that are detected in PMS2 exons 11-15 according to one of 3 categories:
applies to all variants detected in PMS2 exon 15, which are identical to the corresponding exon in PMS2CL. This warning indicates that it is impossible to distinguish a variant listed for PMS2 exon 15 from a variant that may be located in the corresponding exon in pseudogene PMS2CL.
applies to variants detected in PMS2 exon 13 or exon 14, which are very similar to the corresponding exons in PMS2CL and – importantly – where gene conversion is frequently observed. These PMS2 exons may have replaced the corresponding sequence in the PMS2CL pseudogene locus or vice versa. Although PMS2 and PMS2CL sequences can be distinguished in these exons, no high confidence conclusions can be made since the observed PMS2 sequence (and any variants detected in this context) could originate either from the PMS2 gene locus or the PMS2CL pseudogene locus (due to gene conversion).
applies to variants detected in PMS2 exon 12 or exon 11, which are very similar to the corresponding exons in PMS2CL but where gene conversion is rare. Here, the PMS2 sequence can be distinguished from the corresponding PMS2CL sequence with reasonable confidence [e.g. the observed PMS2 sequence (and any variants detected in this context) actually originates from PMS2 and not the PMS2CL pseudogene].