Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants: Application of a points-based ACMG/AMP approach

• Main Authors: Thomassen, Mads, Mesman, Romy L. S., Hansen, Thomas V. O., Menendez, Mireia, Rossing, Maria, Esteban-Sanchez, Ada, Tudini, Emma, Torngren, Therese, Parsons, Michael T., Pedersen, Inge S., Teo, Soo Hwang, Kruse, Torben A., Moller, Pal, Borg, Ake, Jensen, Uffe B., Christensen, Lise L., Singer, Christian F., Muhr, Daniela, Santamarina, Marta, Brandao, Rita, Andresen, Brage S., Feng, Bing-Jian, Canson, Daffodil, Richardson, Marcy E., Karam, Rachid, Pesaran, Tina, LaDuca, Holly, Conner, Blair R., Abualkheir, Nelly, Hoang, Lily, Calleja, Fabienne M. G. R., Andrews, Lesley, James, Paul A., Bunyan, Dave, Hamblett, Amanda, Radice, Paolo, Goldgar, David E., Walker, Logan C., Engel, Christoph, Claes, Kathleen B. M., Machackova, Eva, Baralle, Diana, Viel, Alessandra, Wappenschmidt, Barbara, Lazaro, Conxi, Vega, Ana, Vreeswijk, Maaike P. G., de la Hoya, Miguel, Spurdle, Amanda B.
• Format: Article
• Published: WILEY-HINDAWI 2022
• Subjects: RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Online Access: http://eprints.um.edu.my/46227/; https://doi.org/10.1002/humu.24449
• Institution: Universiti Malaya

Skipping of BRCA2 exon 3 ( increment E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter increment E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted...