Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001032968 | SCV001196275 | likely pathogenic | Bloom syndrome | 2022-09-13 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the helicase and RNase C-terminal (HRDC) domain of the BLM protein, which has been shown to be essential for recruitment of the BLM protein to sites of DNA damage and dissolution of double Holliday junctions (PMID: 22657828, 16876111, 15990871, 22657828). While functional studies have not been performed to directly test the effect of this variant on BLM protein function, this suggests that disruption of this region of the protein is causative of disease. This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is a gross deletion of the genomic region encompassing exon(s) 18-19 of the BLM gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. |