We describe two families with novel variants affecting the developmental gene MAB21L2. First is a missense variant (c.338 G > C; p.[Trp113Ser]) segregating in a family with two half-siblings with microphthalmia, coloboma, lens anomalies, developmental delay and cleft uvula, and the mother with a milder ocular phenotype (optic disc coloboma), developmental delay and microstomia. The gene discussed is MAB21L2; the disease is coloboma.