ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1928G>A (p.Arg643His)

gnomAD frequency: 0.00278  dbSNP: rs12720097
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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000857778 SCV000149195 likely benign not provided 2020-12-01 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327)
CSER _CC_NCGL, University of Washington RCV000211548 SCV000212202 uncertain significance Bloom syndrome 2015-03-11 criteria provided, single submitter research
Invitae RCV000211548 SCV000283117 benign Bloom syndrome 2024-02-01 criteria provided, single submitter clinical testing
Preventiongenetics, part of Exact Sciences RCV000116502 SCV000301735 likely benign not specified criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000116502 SCV000331364 likely benign not specified 2016-08-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000211548 SCV000394415 likely benign Bloom syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Ambry Genetics RCV000565415 SCV000672884 likely benign Hereditary cancer-predisposing syndrome 2018-12-21 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000116502 SCV000916681 benign not specified 2022-10-17 criteria provided, single submitter clinical testing Variant summary: BLM c.1928G>A (p.Arg643His) results in a non-conservative amino acid change located in the Bloom syndrome protein, BDHCT-box associated domain (IPR032439) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0032 in 281568 control chromosomes, predominantly at a frequency of 0.0046 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in BLM causing Bloom Syndrome phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. The variant, c.1928G>A, has been reported in the literature in individuals affected with breast cancer (Thompson_2012, Moradian_2021) and as a somatic events in glioblastoma and Mullerian adenosarcoma (Burzynski_2015, Howitt_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Cancer and/or Bloom Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Nine submitters classified the variant as LB/B while one classified as VUS. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen RCV000857778 SCV001149588 likely benign not provided 2023-10-01 criteria provided, single submitter clinical testing BLM: BP4, BS2
Genome-Nilou Lab RCV000211548 SCV001737334 likely benign Bloom syndrome 2021-06-10 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000857778 SCV002010563 benign not provided 2021-11-03 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000565415 SCV002533680 likely benign Hereditary cancer-predisposing syndrome 2021-06-14 criteria provided, single submitter curation
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000211548 SCV004562959 likely benign Bloom syndrome 2023-10-18 criteria provided, single submitter clinical testing
ITMI RCV000116502 SCV000084399 not provided not specified 2013-09-19 no assertion provided reference population
Genetic Services Laboratory, University of Chicago RCV000116502 SCV000150446 likely benign not specified no assertion criteria provided clinical testing Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000857778 SCV001808140 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000116502 SCV001930149 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000116502 SCV001951297 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000857778 SCV001966492 likely benign not provided no assertion criteria provided clinical testing
Natera, Inc. RCV000211548 SCV002088013 likely benign Bloom syndrome 2017-07-05 no assertion criteria provided clinical testing

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