The accident happened at a Philadelphia home while the mother of the kids was just down the hall in the bathroom, police said.
Jamara Stevens, 11, was killed when she and her three siblings, a 14-year-old boy, 7-year-old girl and 2-year-old boy, were playing with a .357 caliber handgun with an 8-inch barrel in their Mantuna home on Saturday.
Tiffany Goldwire and her four children were in her bedroom, when she went to use the bathroom, police said.
At that point, the children located the loaded firearm, which was left on top of the refrigerator by the mother's boyfriend who visited the home earlier that morning, and the eldest child retrieved it, media reports said.
While playing with the weapon, the 2-year-old boy pointed the loaded, cocked gun in the direction of his 11-year-old sister and it discharged, striking her in the arm, authorities said.
Investigators said the bullet then travelled through her chest, hitting her heart.
The girl was taken to the Children's Hospital of Philadelphia where she was pronounced dead.
This is the latest incident involving children who accidentally shoot someone or die of a self-inflicted gunshot wound.
In October last year, a babysitter in Vidor, Texas, was charged after a 5-year-old toddler she was looking after fatally shot himself with her gun, police said.
Two weeks earlier, a 2-year-old girl fatally shot herself in Fayetteville, North Carolina, and the toddler's father faced involuntary manslaughter charges.
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