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Millions of Americans in the Mid-Atlantic or the Northeast are in for their worst snow of the season as a "significant" storm threatens to wallop the regions later this week, forecasters said.

Forecasting models don't yet agree which specific areas will be hit hardest or when, but a foot of snow could hit the so-called Northeast Megalopolis — Boston, New York, Philadelphia, Baltimore and Washington, D.C. — on Friday or Saturday, with the potential for some areas northwest of Interstate 95 to get as much as 2 feet, the National Weather Service said late Tuesday afternoon.

As if that weren't enough, a poorly timed full moon could also mean flooding in coastal regions in the East, NBC News meteorologist Bill Karins said.

Kevin Roth, lead meteorologist for The Weather Channel, said: "Winter is ramping up. For many areas, this will be the biggest snowfall of the season so far, and for some it could be the biggest they will have all year. It will be significant."

In the meantime, a widespread chill has already brought sub-freezing temperatures from the Midwest to the East Coast and as far south as northern Florida, while a separate low-pressure system is set to pummel the eastern Plains and Missouri with up to 5 inches of snow by the middle of the week.

Minneapolis temperatures hovered around zero on Tuesday, and wind chills all the way down to minus-40 are forecast for parts of the Dakotas and other parts of Minnesota, the National Weather Service said.

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Significant #snow is still possible from DC to Boston late this week, latest info here: https://t.co/Skf4tbzH0Q pic.twitter.com/pStUoTp6zv — The Weather Channel (@weatherchannel) January 19, 2016

About 70 percent of the population woke up to below freezing temperatures Tuesday, said Kathryn Prociv, a meteorologist for The Weather Channel .

The Northeast won't get a break, either. Temperatures are expected to stick at 10 to 15 degrees below average there, Prociv said.

For the Mid-Atlantic and the Northeast, Friday evening's commute could be messy or even hazardous, depending on when the major snow arrives.

"The disturbance causing it is still out in the Pacific," Roth said. "Once it hits the West Coast ... and gets inland, we might have a better idea on the timing and where the heaviest snow is likely to occur."

Forecasts currently suggest that the Mid-Atlantic — particularly West Virginia and Pennsylvania — will see the heaviest snow.

"But the Northeast is not off the hook yet," Roth said. "It could shift northward more towards New England later this week."

He added: "Of the two longer-range models, one has it being heavy snow on Friday night then tapering off into Saturday; the other has it heavy on Saturday tapering off into Sunday, so there are minor timing differences."

Many of the main cities in the East— including New York, Boston, Philadelphia and Washington — are at snow deficits compared with past year averages, but the coming snow could completely make up for those deficits, according to The Weather Channel.

Here is a satellite image of the storm that is forecast to reach the East Coast by Friday, along with forecast track pic.twitter.com/c1Q6ySbUmz — NWS WPC (@NWSWPC) January 19, 2016

In the Ohio Valley, the Tennessee Valley and the Appalachians, the snow could start as early as Thursday.

Meanwhile, the country's midsection was grappling with lighter snow and bone-chilling cold all the way from the Midwest as far south as northern Florida.

Volunteers of America Michigan added overflow beds Monday night at its shelter in Lansing, where temperatures were already in the single digits.

"You've got to find a spot for everybody, because you can die tonight from exposure," Patrick Patterson, the organization's executive vice president, told NBC station WILX. "That's as simple as it gets. We're just trying to keep people safe tonight."

At Bob Hamilton Plumbing & Heating in Kansas City, Missouri, "the phone has been ringing all day long," owner Bob Hamilton told NBC station KSHB. "It's not something that's going to go away, because the cold is here."