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He came on as a second-half substitute after replacing left-back Matias Vina in the 57th minute of the game.
Afena-Gyan partnered Tammy Abraham up front as Roma came from behind to record a 2-1 win over Cagliari.
Mourinho side’s had to dig deep to secure the three points after falling behind to Leonardo Pavoletti’s strike early in the second half.
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However, goals from Roger Ibanez and Lorenzo Pellegrini in the final 20 minutes helped the Giallorossi overturn the score.
In the aftermath of the game, Mourinho reveled in the victory and gave Afena-Gyan a shout out in an Instagram post.
The teenager has been in impressive form for AS Roma’s U19 team since joining the club in January, and has scored four goals this season.
The young centre-forward earned his first call-up to the senior team in September and was again invited to train with them during the October international break.
Mourinho seems to be a huge fan of Afena-Gyan, with the striker demonstrating his quality and consistency in the youth team.
Having now earned his senior debut for Roma, the Ghanaian will be hoping for more opportunities under the Portuguese manager.