Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001020616 | SCV001182120 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-07-31 | criteria provided, single submitter | clinical testing | The c.3564delC variant, located in coding exon 18 of the BLM gene, results from a deletion of one nucleotide at nucleotide position 3564, causing a translational frameshift with a predicted alternate stop codon (p.F1189Lfs*10). This alteration is also known as c.3564del in the literature. This alteration has been detected in the compound heterozygous state in an infant small for gestational age with growth deficiency, microcephaly, a triangular face, micrognathia, developmental delay, mitral regurgitation and hyperpigmented skin in a study of 114 Chinese children who underwent whole exome sequencing and chromosomal microarray analysis for the indication of short stature (Huang Z et al. Cell. Physiol. Biochem., 2018 Aug;49:295-305). 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. |
| Labcorp Genetics |
RCV002549519 | SCV003443322 | pathogenic | Bloom syndrome | 2022-03-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe1189Leufs*10) 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). This variant is present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with clinical features of Bloom syndrome (PMID: 30138938). ClinVar contains an entry for this variant (Variation ID: 823933). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV002549519 | SCV004210834 | pathogenic | Bloom syndrome | 2023-10-28 | criteria provided, single submitter | clinical testing |