Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV004555211 | SCV005044181 | likely pathogenic | Ververi-Brady syndrome | 2023-01-26 | criteria provided, single submitter | clinical testing | This 17.28 kb duplication in QRICH1 has not previously been reported in the literature or public variant repositories (ClinVar and LOVD), and is absent from population databases (gnomAD SVs v2.1and DGV), suggesting it is not a common benign variant in the populations represented in those databases. The duplication is apparently tandem per split reads spanning the breakpoints, and it encompasses the entire exon 3 and parts of introns 2 and 3 of this 9-exon gene. Should only exon 3 of this duplication is incorporated in the transcription, the open reading frame would be preserved but the protein length would increase by ~45%, however, the open reading frame might be disrupted should additional genomic sequences are also incorporated in the transcription which might result in loss-of-function via nonsense mediated decay. Based on available evidence this de novo intragenic tandem duplication in QRICH1 is classified as Likely pathogenic. |