ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1284G>A (p.Trp428Ter) (rs1057516964)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410691 SCV000486511 likely pathogenic Bloom syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000410691 SCV000916680 pathogenic Bloom syndrome 2017-12-29 criteria provided, single submitter clinical testing Variant summary: The BLM c.1284G>A (p.Trp428X) variant results in a premature termination codon, predicted to cause a truncated or absent BLM 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 (e.g. c.1544delA (p.Asn515fsX16), c.1642C>T (p.Gln548X), and c.1933C>T (p.Gln645X)). This variant is absent in 245796 control chromosomes (gnomAD). A publication, German_2007, cites the variant in two compound heterozygote Bloom Syndrome patients. In addition, a clinical diagnostic laboratory classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000410691 SCV000942374 pathogenic Bloom syndrome 2018-09-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp428*) in the BLM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another BLM variant in several individuals affected with Bloom syndrome (PMID: 17407155, 29098565). ClinVar contains an entry for this variant (Variation ID: 371048). Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). For these reasons, this variant has been classified as Pathogenic.

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