Probably benign. Predicted to be damaging by Polyphen 2 and other damaging variants cause Alagille syndrome, but this variant is not rare enough and has been seen in a healthy PGP participant.
This variant is predicted to be damaging by Polyphen 2, but has been seen heterozygously in 2 out of 23 PGP + public genomes. Other variants in NOTCH2 are reported to cause Alagille syndrome (1 in 70,000 prevalence) in a dominant manner. The presence of this gene in a healthy PGP participant, and was seen in 2 out of 46 random PGP + public alleles, contradicting this variant as having a significant high penetrance pathogenic effect, and so we tentatively evaluate it as benign.
Even if a hypothetical pathogenic variant had only had moderate penetrance for causing Alagille syndrome (1%) and were responsible for 50% of cases, such a variant would have a frequency of .07% and the chances of seeing it twice in 46 random alleles would be p=0.00052.