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Manchester United legend Giggs, 48, temporarily stepped away from the role in 2020 after he was charged with assaulting his ex-girlfriend, Kate Greville.
Giggs, who strenuously denies the allegations against him, has now quit the job permanently as he awaits his day in court.
In a statement, Giggs said: "After much consideration, I am standing down from my position as manager of the Wales men's national team with immediate effect.
"It has been an honour and a privilege to manage my country, but it is only right that the Wales FA, the coaching staff and the players prepare for the tournament with certainty, clarification and without speculation around the position of their head coach."
The decision comes after talks between Giggs and the Football Association of Wales (FAW), and follows the country's qualification for the 2022 World Cup under interim boss Rob Page.
Page, who has been in charge of the Wales for the last two years, successfully guided his nation to their first World Cup for 64 years with a 1-0 victory over Ukraine in last month's play-off.
Giggs was initially due to face trial on January 17 but the court case was adjourned until August 8 due to a lack of space at Manchester Crown Court.
He is accused of causing Greville actual bodily harm at his home in Worsley, Greater Manchester in November 2020 and using coercive behaviour towards her.
The former Wales captain has also been accused of assaulting his ex's sister, Emma. Giggs denies all of the allegations.
According to the Daily Mail, Giggs came to the decision to step down as manager of Wales as he did not want his situation to be a distraction for the team as they prepare for their first World Cup since 1958.
Following Giggs' announcement, the FAW released its own statement which read: "The FAW places on record its gratitude to Ryan Giggs for his tenure as manager of the Cymru men's national team and appreciates the decision he has taken, which is in the best interests of Welsh football."
"The full focus of the FAW and the Cymru men's national team is on the FIFA World Cup in Qatar later this year."
Page, 47, confirmed earlier this month that his contract with Wales had been extended to allow him to take charge of the team in Qatar.
He could now be appointed as Wales permanent manager after impressing in his role as interim boss.
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