Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000598767 | SCV000225477 | pathogenic | not provided | 2014-07-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000598767 | SCV000709964 | pathogenic | not provided | 2017-12-18 | criteria provided, single submitter | clinical testing | The c.2407dupT variant in the BLM gene has been previously reported previously in the heterozygous state in at least two individuals with Bloom syndrome. Information on a second variant in these individuals was not specified (German et al., 2007). This duplication causes a frameshift starting with codon Tryptophan 803, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Trp803LeufsX4. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider c.2407dupT to be pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000035004 | SCV001363837 | pathogenic | Bloom syndrome | 2019-10-28 | criteria provided, single submitter | clinical testing | Variant summary: BLM c.2407dupT (p.Trp803LeufsX4) 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. The variant allele was found at a frequency of 4e-06 in 251410 control chromosomes (gnomAD). c.2407dupT has been reported in the literature in individuals affected with Bloom Syndrome (German_2007). Two ClinVar submitters including a reputable database (Gene Reviews) (evaluation after 2014) cite the variant as pathogenic. Furthermore, Gene Reviews reports the variant as the second most common pathogenic variant for Bloom Syndrome in the Ashkenazi Jewish population (Flanagan_2019). Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000035004 | SCV002229157 | pathogenic | Bloom syndrome | 2021-04-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Bloom syndrome (PMID: 17407155). ClinVar contains an entry for this variant (Variation ID: 42177). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp803Leufs*4) 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). |
Gene |
RCV000035004 | SCV000058643 | not provided | Bloom syndrome | no assertion provided | literature only | ||
Counsyl | RCV000035004 | SCV001132142 | likely pathogenic | Bloom syndrome | 2015-04-28 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000035004 | SCV002088066 | pathogenic | Bloom syndrome | 2017-09-22 | no assertion criteria provided | clinical testing |