Canonical Splice Site variants
PVS1 was weighted for splicing variants predicted to produce an exon
skipping with a subsequent frameshift. PM2 was weighted for
c.593-1G>T and c.792+2T>C. Neither of them
received PP3 to avoid redundancy with PVS1, remaining as LP according to
ACMG and ClinGen-TP53 frameworks. Notwithstanding, the
combination of these rules in the Bayes model gives a posterior
probability of 0.994, allowing its classification as P (Tavtigian et
al., 2018). c.792+2T>C was reported in a previous study
from our group (Feliubadaló et al., 2017), it produces a partial
retention of intron 6, decreasing the expression of wildtype. It is
classified as LP by ClinVar.