ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.615G>A (p.Lys205=) (rs28903082)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573446 SCV000672868 likely benign Hereditary cancer-predisposing syndrome 2016-11-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
GeneDx RCV000123841 SCV000167184 benign not specified 2014-01-06 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago RCV000123841 SCV000593632 likely benign not specified 2016-08-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000123841 SCV000916685 benign not specified 2018-08-13 criteria provided, single submitter clinical testing Variant summary: BLM c.615G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0016 in 276156 control chromosomes, predominantly within the African subpopulation at a frequency of 0.017 in the gnomAD database, including 3 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 4.8 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 African origin. To our knowledge, no occurrence of c.615G>A in individuals affected with Bloom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000234095 SCV000283152 benign Bloom syndrome 2018-01-13 criteria provided, single submitter clinical testing

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