ClinVar Miner

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

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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 2019-12-19 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.
Institute of Human Genetics, University of Leipzig Medical Center RCV000410691 SCV001440408 pathogenic Bloom syndrome 2019-01-01 criteria provided, single submitter clinical testing This variant was identified as compound heterozygous.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.