ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1490A>C (p.Gln497Pro) (rs368547042)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000550747 SCV000898547 uncertain significance Bloom syndrome 2017-08-11 criteria provided, single submitter clinical testing BLM NM_000057.3 exon7 p.Gln497Pro (c.1490A>C): This variant has not been reported in the literature but is present in 37/33556 Latino chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs368547042). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. Of note, 4 species also carry this variant (Tenrec, Opossum, Tasmanian devil, Wallaby), further suggesting that this variant may not be damaging. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Fulgent Genetics,Fulgent Genetics RCV000550747 SCV000896482 uncertain significance Bloom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000550747 SCV000623241 uncertain significance Bloom syndrome 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 497 of the BLM protein (p.Gln497Pro). The glutamine residue is weakly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is present in population databases (rs368547042, ExAC 0.1%) but has not been reported in the literature in individuals with a BLM-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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