Alternative splicing and ACMG-AMP-2015-based classification of PALB2 genetic variants: an ENIGMA report.
Irene Lopez-PerolioRaphaël LemanRaquel BeharVanessa LattimoreJohn F PearsonLaurent CastéraAlexandra MartinsDominique VaurNicolas GoardonGrégoire DavyPilar GarreVanesa García-BarberánPatricia LlovetPedro Pérez-SeguraEduardo Díaz-RubioTrinidad CaldésKathleen S HruskaVickie HsuanSitao WuTina PesaranRachid KaramJohan Vallon-ChristerssonAke Borgnull nullAlberto Valenzuela-PalomoEladio A VelascoMelissa SoutheyMaaike P G VreeswijkPeter DevileeAnders KvistAmanda B SpurdleLogan C WalkerSophie KriegerMiguel de la HoyaPublished in: Journal of medical genetics (2019)
PVS1 is not necessarily warranted for splice site variants targeting four PALB2 acceptor sites (exons 2, 5, 7 and 10). As a result, rare variants at these splice sites cannot be assumed pathogenic/likely pathogenic without further evidences. Our study puts a warning in up to five PALB2 genetic variants that are currently reported as pathogenic/likely pathogenic in ClinVar.