Fig. 2: Characterization of somatic mosaicism of NF1 PVs in the PMBB and Ambry datasets. | Nature Communications

Fig. 2: Characterization of somatic mosaicism of NF1 PVs in the PMBB and Ambry datasets.

From: A genotype-first approach identifies high incidence of NF1 pathogenic variants with distinct disease associations

Fig. 2

A The variant allele fraction (VAF) for each NF1 PV identified in individuals in the Clinical-NF1 group (left, blue, n = 22) and PV-Only group (right, pink, n = 34) are displayed for PMBB. Box plots illustrate the median, first and third quartiles, minimum, and maximum for each group. Individuals for whom VAF could nto be determined are excluded. The difference in means between the two groups was statistically significant by 2-sided linear regression (p = 4.54e-06). B Comparison of NF1 PV VAF, as in (A), but for the Ambry data; individuals in the Clinical-NF1 group (n = 145) are shown on the left in green and individuals in the PV-Only group (n = 112) are shown on the right in orange. Individuals for whom VAF could not be determined are excluded. Box plots illustrate the median, first and third quartiles, minimum, and maximum for each group. The difference in means between the two groups was statistically significant by 2-sided linear regression (p = 7.1e12). C 2-sided linear regression of patient age, in years (horizontal axis), against NF1 PV VAF (vertical axis) for the PMBB PV-Only group. Each point represents a single individual. The regression line is shown, with gray shading illustrating the 95% confidence intervals. There is no significant correlation between the two variables (Pearson correlation coefficient of −0.03, p = 0.66). D 2-sided linear regression of patient age against NF1 PV VAF as in (B), but for the 47 Ambry PV-Only patients with a mosaic NF1 PV. Each point represents a single individual. The regression line is shown, with gray shading illustrating the 95% confidence intervals. There is no significant correlation between the two variables (Pearson correlation coefficient of −0.02, p = 0.64). E The distribution of patient ages at time of genetic testing, in years (horizontal axis) for all 43,559 PMBB participants without an NF1 PV (gray) and for the 35 individuals in the PMBB PV-Only group (pink). There is no significant difference in the distribution of patient ages between the two groups by the 2-sided Wilcoxon rank sum test (p = 0.11). F The distribution of patient ages at time of genetic testing for all 118,709 Ambry patients tested with MGPTs containing the NF1 gene (gray) and the 46 individuals in the Ambry PV-Only group with confirmed mosaic NF1 PVs (orange). The Ambry PV-Only group with mosaic NF1 PVs is significantly older than the overall Ambry cohort by the 2-sided Wilcoxon rank sum test (p = 4.3e-06).

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