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These data provide evidence for the first time in a cancer-predisposition gene, that certain presumed null variants can retain function due to their impact on splicing. Further studies are required to estimate cancer-risk associated with these hypomorphic variants. More generally, our findings highlight the need to exercise caution in the interpretation of putative LoF variants susceptible to induce in-frame splicing modifications. Copyright ©2020, American Association for Cancer Research.Worldwide, it is estimated that about 1.3 million n
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