ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2580_2581del (p.His860fs) (rs864622347)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204244 SCV000260242 pathogenic Bloom syndrome 2019-10-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His860Glnfs*12) in the BLM gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with BLM-related disease. ClinVar contains an entry for this variant (Variation ID: 220018). Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000204244 SCV001467764 likely pathogenic Bloom syndrome 2020-12-07 criteria provided, single submitter clinical testing Variant summary: BLM c.2580_2581delTA (p.His860GlnfsX12) 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 allele was found at a frequency of 8e-06 in 251222 control chromosomes. To our knowledge, no occurrence of c.2580_2581delTA in individuals affected with Bloom Syndrome and no experimental evidence demonstrating its impact on protein function have 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.

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