ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.410A>G (p.Lys137Arg) (rs28384988)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575143 SCV000672877 benign Hereditary cancer-predisposing syndrome 2018-03-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene,General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000437672 SCV000511441 likely benign not provided 2016-05-23 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000120236 SCV000331616 benign not specified 2015-07-29 criteria provided, single submitter clinical testing
GeneDx RCV000120236 SCV000167181 benign not specified 2014-02-06 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.
ITMI RCV000120236 SCV000084384 not provided not specified 2013-09-19 no assertion provided reference population
Integrated Genetics/Laboratory Corporation of America RCV000120236 SCV000918650 benign not specified 2018-04-06 criteria provided, single submitter clinical testing Variant summary: BLM c.410A>G (p.Lys137Arg) results in a conservative amino acid change located in the Bloom syndrome protein, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 277122 control chromosomes, predominantly at a frequency of 0.014 within the African subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 3.96 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.410A>G in individuals affected with Bloom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four 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 RCV000475446 SCV000555830 benign Bloom syndrome 2018-01-04 criteria provided, single submitter clinical testing

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