Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012779 | SCV001173279 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-10 | criteria provided, single submitter | clinical testing | The p.W567* pathogenic mutation (also known as c.1701G>A), located in coding exon 6 of the BLM gene, results from a G to A substitution at nucleotide position 1701. This changes the amino acid from a tryptophan to a stop codon within coding exon 6. This alteration has been previously identified in an individual with Bloom syndrome in conjunction with another truncating alteration (p.R364*); phase (cis or trans) of the two alterations was not determined (German J et al. Hum. Mutat., 2007 Aug;28:743-53). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194354 | SCV001363839 | likely pathogenic | Bloom syndrome | 2021-10-20 | criteria provided, single submitter | clinical testing | Variant summary: BLM c.1701G>A (p.Trp567X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 216282 control chromosomes. c.1701G>A has been reported in the literature in a compound heterozygote individual affected with Bloom Syndrome (German_2007). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV001194354 | SCV002159804 | pathogenic | Bloom syndrome | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp567*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Bloom syndrome (PMID: 17407155). ClinVar contains an entry for this variant (Variation ID: 819865). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001194354 | SCV004210913 | pathogenic | Bloom syndrome | 2023-03-16 | criteria provided, single submitter | clinical testing |