Total submissions: 20
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
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, |
RCV000116502 | SCV000301735 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Eurofins Ntd Llc |
RCV000116502 | SCV000331364 | likely benign | not specified | 2016-08-01 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
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, |
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. |
Ce |
RCV000857778 | SCV001149588 | likely benign | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | BLM: BP4, BS2 |
Genome- |
RCV000211548 | SCV001737334 | likely benign | Bloom syndrome | 2021-06-10 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000857778 | SCV002010563 | benign | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000565415 | SCV002533680 | likely benign | Hereditary cancer-predisposing syndrome | 2021-06-14 | criteria provided, single submitter | curation | |
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, |
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, |
RCV000857778 | SCV001808140 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000116502 | SCV001930149 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000116502 | SCV001951297 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000857778 | SCV001966492 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Natera, |
RCV000211548 | SCV002088013 | likely benign | Bloom syndrome | 2017-07-05 | no assertion criteria provided | clinical testing |