Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000411706 | SCV000623290 | likely pathogenic | Bloom syndrome | 2024-01-07 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 14 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with colorectal cancer (PMID: 28195393). ClinVar contains an entry for this variant (Variation ID: 371621). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Ambry Genetics | RCV002436232 | SCV002746679 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | The c.2824-2A>T intronic variant results from an A to T substitution two nucleotides upstream from coding exon 14 in the BLM gene. This alteration was reported as a likely pathogenic variant detected in one individual from a cohort of individuals with familial colorectal cancer who previously had negative germline testing for the Lynch syndrome genes (Hansen MF et al. Clin. Genet., 2017 Feb). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Counsyl | RCV000411706 | SCV000487245 | likely pathogenic | Bloom syndrome | 2016-10-31 | no assertion criteria provided | clinical testing | |
| Natera, |
RCV000411706 | SCV002088123 | likely pathogenic | Bloom syndrome | 2017-11-09 | no assertion criteria provided | clinical testing |