Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000826136 | SCV000967656 | pathogenic | Deafness-infertility syndrome; Rare genetic deafness | 2018-02-24 | criteria provided, single submitter | clinical testing | The exon 7 CATSPER2 deletion was identified by a ddPCR probe targeting exon 7 of CATSPER2 and, at a minimum, encompasses this region in the CATSPER2 gene. Exact breakpoints of the detected deletion could not be determined due to limitations of the testing methodology. Therefore, this assay cannot determine if this vari ant represents a larger deletion encompassing the entire CATSPER2 gene region an d/or whether the neighboring STRC gene is also impacted. Our assay can identify whole gene deletions of STRC and exon level deletions impacting exons 23-25, but due to high STRC/pseudogene sequence homology and the limitations of this assay , we cannot rule out the possibility that this deletion extends into upstream ex ons in STRC that are nearer to CATSPER2. Contiguous gene deletions encompassing both the STRC and CATSPER2 genes have been reported in several individuals with hearing loss (Verpy 2001, Zhang 2007, Knijnenburg 2009, Francey 2011). Homozygou s or compound heterozygous deletions that affect both of these genes are associa ted with deafness and male infertility syndrome (DIS; Zhang 2007). Both copies o f CATSPER2 must be affected for a male individual to have infertility. In additi on, bi-allelic loss of function variants that impact only CATSPER2 have been rep orted in individuals with nonsyndromic autosomal recessive male infertility (Ave narius 2009). In summary, based on the expected effect on the protein and the re ported cases of individuals with deletions and variants impacting the CATSPER2 g ene, this copy number variant meets our criteria to be classified as pathogenic for autosomal recessive male infertility, and given the limitations of this assa y it is unclear if this CNV impacts the neighboring deafness-related STRC gene. ACMG/AMP Criteria applied: PVS1, PM3. |