Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001231693 | SCV001404224 | pathogenic | Bloom syndrome | 2023-08-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). ClinVar contains an entry for this variant (Variation ID: 42072). This premature translational stop signal has been observed in individual(s) with Bloom syndrome (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. This sequence change creates a premature translational stop signal (p.Trp881*) in the BLM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). |
Ambry Genetics | RCV002426543 | SCV002743390 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-07-06 | criteria provided, single submitter | clinical testing | The p.W881* pathogenic mutation (also known as c.2643G>A), located in coding exon 12 of the BLM gene, results from a G to A substitution at nucleotide position 2643. This changes the amino acid from a tryptophan to a stop codon within coding exon 12. This variant has been detected in the homozygous state in an individual diagnosed with Bloom syndrome (Renes JS et al. J Clin Endocrinol Metab, 2013 Oct;98:3932-8). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Baylor Genetics | RCV001231693 | SCV004210842 | pathogenic | Bloom syndrome | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Service de Génétique Moléculaire, |
RCV001231693 | SCV001432297 | pathogenic | Bloom syndrome | no assertion criteria provided | clinical testing | ||
Natera, |
RCV001231693 | SCV002088097 | pathogenic | Bloom syndrome | 2017-03-16 | no assertion criteria provided | clinical testing |