Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001377320 | SCV001574626 | likely pathogenic | Bloom syndrome | 2022-11-04 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1066346). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 13 of the BLM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). |
Baylor Genetics | RCV001377320 | SCV004210875 | likely pathogenic | Bloom syndrome | 2023-07-20 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004728692 | SCV005339336 | likely pathogenic | BLM-related disorder | 2024-07-18 | no assertion criteria provided | clinical testing | The BLM c.2662+2T>G variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant is predicted to impact splicing at the consensus donor site based on splicing prediction programs (SpliceAI, Jaganathan K, et al. 2019. PubMed ID: 30661751). To our knowledge, this variant has not been reported in the literature. This variant has not been reported in a large population database, indicating this variant is rare. This variant has been interpreted as likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1066346/). Variants that disrupt the consensus splice donor site in BLM are expected to be pathogenic. This variant is interpreted as likely pathogenic. |