ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3028del (p.Asp1010fs) (rs780379121)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169440 SCV000220857 likely pathogenic Bloom syndrome 2014-11-06 criteria provided, single submitter literature only
Invitae RCV000169440 SCV000623297 pathogenic Bloom syndrome 2020-03-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp1010Metfs*24) in the BLM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs780379121, ExAC 0.003%). This variant has been reported in individuals affected with Bloom syndrome (PMID: 17407155). ClinVar contains an entry for this variant (Variation ID: 189048). Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000574982 SCV000672986 pathogenic Hereditary cancer-predisposing syndrome 2017-07-14 criteria provided, single submitter clinical testing The c.3028delG pathogenic mutation, located in coding exon 15 of the BLM gene, results from a deletion of one nucleotide at nucleotide position 3028, causing a translational frameshift with a predicted alternate stop codon (p.D1010Mfs*24). This alteration has been reported in three individuals with Bloom syndrome (German J et al. Hum. Mutat., 2007 Aug;28:743-53). 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, LabCorp RCV000169440 SCV001363838 pathogenic Bloom syndrome 2019-06-17 criteria provided, single submitter clinical testing Variant summary: BLM c.3028delG (p.Asp1010MetfsX24) 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 1.2e-05 in 248358 control chromosomes (gnomAD). c.3028delG has been reported in the literature in a homozygous and compound heterozygote individuals affected with Bloom Syndrome (German_2007). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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