Implementing genome and exome sequencing in clinical practice presents challenges, including obtaining meaningful informed consent. Consent may be challenging due to test limitations such as uncertainties associated with test results and interpretation, complexity created by the potential for additional findings and high patient expectations. We drew on the experiences of research teams within the Clinical Sequencing Exploratory Research (CSER1) Consortium on informed consent for clinical genome and exome sequencing (CGES) to negotiate consensus considerations. We present six considerations for clinicians and 12 key points to communicate as they support patients in deciding whether to undergo CGES. These considerations and key points provide a helpful starting point for informed consent to CGES, grounded in the Clinical Sequencing Exploratory Research (CSER1) experience.