Submissions for variant NC_000006.11:g.(?_162683537)_(162683817_?)dup

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001861924	SCV002236269	pathogenic	not provided	2022-09-13	criteria provided, single submitter	clinical testing	This variant results in a copy number gain of the genomic region encompassing exon(s) 3 of the PRKN gene. While the exact position of this variant cannot be determined from the data, sub-genic copy number gains are generally in tandem (PMID: 25640679). This variant is predicted to be out-of-frame, and may result in an absent or disrupted protein product. Loss-of-function variants in PRKN are known to be pathogenic (PMID: 10072423, 20301651, 22956510). A similar copy number variant has been observed in individual(s) with PRKN-related early-onset Parkinson's disease (PMID: 10824074; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. For these reasons, this variant has been classified as Pathogenic.
Invitae	RCV000707828	SCV000836938	likely pathogenic	Autosomal recessive juvenile Parkinson disease 2	2018-05-07	flagged submission	clinical testing	This variant results in a copy number gain of the genomic region encompassing exon 3 of the PARK2 gene. While the exact position of this variant cannot be determined from this data, sub-genic copy number gains are generally in tandem (PMID: 25640679) and may result in an absent or disrupted protein product. This variant has been observed in two individuals affected with early-onset Parkinson's disease, and to be homozygous in one of these two individuals (PMID: 10824074). Loss-of-function variants in PARK2 are known to be pathogenic (PMID: 10072423, 20301651, 22956510). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.