ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2407dup (p.Trp803fs) (rs367543012)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000598767 SCV000225477 pathogenic not provided 2014-07-14 criteria provided, single submitter clinical testing
GeneDx 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, LabCorp 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.
GeneReviews RCV000035004 SCV000058643 pathogenic Bloom syndrome 2019-02-19 no assertion criteria provided literature only
Counsyl RCV000035004 SCV001132142 likely pathogenic Bloom syndrome 2015-04-28 no assertion criteria provided clinical testing

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