ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3667dup (p.Thr1223fs)

gnomAD frequency: 0.00001  dbSNP: rs1057517154
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410178 SCV000486834 likely pathogenic Bloom syndrome 2016-08-18 criteria provided, single submitter clinical testing
Invitae RCV000410178 SCV001591917 pathogenic Bloom syndrome 2023-06-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr1223Asnfs*20) 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). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 371288). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 24448499). This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV002450947 SCV002617728 pathogenic Hereditary cancer-predisposing syndrome 2022-07-28 criteria provided, single submitter clinical testing The c.3667dupA pathogenic mutation, located in coding exon 18 of the BLM gene, results from a duplication of A at nucleotide position 3667, causing a translational frameshift with a predicted alternate stop codon (p.T1223Nfs*20). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 RCV000410178 SCV004210868 likely pathogenic Bloom syndrome 2023-08-14 criteria provided, single submitter clinical testing

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