Person:

Harrison, Steven

In this Letter to the Editor, potentially flawed conclusions of a recent study are discussed.

Purpose Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and reassessment resolves interpretation differences by analyzing a subset of variants. Methods: ClinVar variants with submissions from at least two of the four participating laboratories were compared. For a subset of identified differences, laboratories documented the basis for discordance, shared internal data, independently reassessed with the ACMG-AMP guidelines, and then compared interpretations. Results: 6,169 variants in ClinVar were interpreted by at least two of the participating laboratories, of which 88.3% were initially concordant. Laboratories reassessed 242/724 initially discordant variants, of which 87.2% (211) were resolved by reassessment with current criteria and/or internal data sharing. 12.8% (31) of reassessed variants remain discordant due to differences in application of the ACMG-AMP guidelines. Conclusion: Participating laboratories increased their overall concordance from 88.3% to 91.7%, indicating that sharing variant interpretations in ClinVar, allowing identification of differences and motivation to resolve those differences, is critical to move toward more consistent variant interpretations.

We present the strongest constraints to date on anisotropies of cosmic microwave background (CMB) polarization rotation derived from 150 GHz data taken by the BICEP2 & Keck Array CMB experiments up to and including the 2014 observing season (BK14). The definition of the polarization angle in BK14 maps has gone through self-calibration in which the overall angle is adjusted to minimize the observed TB and EB power spectra. After this procedure, the QU maps lose sensitivity to a uniform polarization rotation but are still sensitive to anisotropies of polarization rotation. This analysis places constraints on the anisotropies of polarization rotation, which could be generated by CMB photons interacting with axionlike pseudoscalar fields or Faraday rotation induced by primordial magnetic fields. The sensitivity of BK14 maps (∼3  μK−arc min) makes it possible to reconstruct anisotropies of the polarization rotation angle and measure their angular power spectrum much more precisely than previous attempts. Our data are found to be consistent with no polarization rotation anisotropies, improving the upper bound on the amplitude of the rotation angle spectrum by roughly an order of magnitude compared to the previous best constraints. Our results lead to an order of magnitude better constraint on the coupling constant of the Chern-Simons electromagnetic term gaγ≤7.2×10−2/HI (95% confidence) than the constraint derived from the B-mode spectrum, where HI is the inflationary Hubble scale. This constraint leads to a limit on the decay constant of 10−6≲fa/Mpl at mass range of 10−33≤ma≤10−28  eV for r=0.01, assuming gaγ∼α/(2πfa) with α denoting the fine structure constant. The upper bound on the amplitude of the primordial magnetic fields is 30 nG (95% confidence) from the polarization rotation anisotropies.