ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3847C>T (p.Gln1283Ter)

dbSNP: rs367543031
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000034915 SCV000623319 pathogenic Bloom syndrome 2023-09-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1283*) 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 present in population databases (rs367543031, gnomAD 0.003%). 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: 42089). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000034915 SCV002500247 pathogenic Bloom syndrome 2022-03-09 criteria provided, single submitter clinical testing Variant summary: BLM c.3847C>T (p.Gln1283X) 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 251478 control chromosomes. c.3847C>T has been reported in the literature as a homozygous genotype in at-least one in individual affected with Bloom Syndrome (example, German_2007). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Ambry Genetics RCV002354185 SCV002621693 pathogenic Hereditary cancer-predisposing syndrome 2022-07-28 criteria provided, single submitter clinical testing The p.Q1283* pathogenic mutation (also known as c.3847C>T), located in coding exon 19 of the BLM gene, results from a C to T substitution at nucleotide position 3847. This changes the amino acid from a glutamine to a stop codon within coding exon 19. This variant was reported in a homozygous state in 1/134 patients from a Bloom syndrome registry (German J et al. Hum. Mutat. 2007 Aug;28:743-53). In a pan-ethnic population screen for Bloom syndrome carrier status, this variant was reported in 3/22864 individuals (Perreault-Micale C et al. Mol Genet Genomic Med. 2015 Jul;3:363-73). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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.
Baylor Genetics RCV000034915 SCV004210898 pathogenic Bloom syndrome 2023-04-16 criteria provided, single submitter clinical testing
Counsyl RCV000034915 SCV000793460 likely pathogenic Bloom syndrome 2017-08-16 no assertion criteria provided clinical testing
Natera, Inc. RCV000034915 SCV002090616 pathogenic Bloom syndrome 2017-03-16 no assertion criteria provided clinical testing

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